CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway

Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Zhang, Xu [verfasserIn] Guo, Yeye Xiao, Ta Li, Jie Guo, Aiyuan Lei, Li Jin, Chong Long, Qi Su, Juan Yin, Mingzhu Liu, Hong Chen, Chao Zhou, Zhe Zhu, Susi Tao, Juan Hu, Shuo Chen, Xiang Peng, Cong

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	CD147, Keratinocyte, Malignant transformation, RSK2

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: Journal of experimental & clinical cancer research - Berlin : Springer, 2008, 41(2022), 1 vom: 13. Aug.
Übergeordnetes Werk:	volume:41 ; year:2022 ; number:1 ; day:13 ; month:08

Links:	Volltext

DOI / URN:	10.1186/s13046-022-02427-w

Katalog-ID:	SPR050923277

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520			\|a Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway.
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allfields	10.1186/s13046-022-02427-w doi (DE-627)SPR050923277 (SPR)s13046-022-02427-w-e DE-627 ger DE-627 rakwb eng Zhang, Xu verfasserin aut CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. CD147, Keratinocyte, Malignant transformation, RSK2 (dpeaa)DE-He213 Guo, Yeye aut Xiao, Ta aut Li, Jie aut Guo, Aiyuan aut Lei, Li aut Jin, Chong aut Long, Qi aut Su, Juan aut Yin, Mingzhu aut Liu, Hong aut Chen, Chao aut Zhou, Zhe aut Zhu, Susi aut Tao, Juan aut Hu, Shuo aut Chen, Xiang (orcid)0000-0001-8187-636X aut Peng, Cong (orcid)0000-0001-7104-5490 aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 41(2022), 1 vom: 13. Aug. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:41 year:2022 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13046-022-02427-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2022 1 13 08
spelling	10.1186/s13046-022-02427-w doi (DE-627)SPR050923277 (SPR)s13046-022-02427-w-e DE-627 ger DE-627 rakwb eng Zhang, Xu verfasserin aut CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. CD147, Keratinocyte, Malignant transformation, RSK2 (dpeaa)DE-He213 Guo, Yeye aut Xiao, Ta aut Li, Jie aut Guo, Aiyuan aut Lei, Li aut Jin, Chong aut Long, Qi aut Su, Juan aut Yin, Mingzhu aut Liu, Hong aut Chen, Chao aut Zhou, Zhe aut Zhu, Susi aut Tao, Juan aut Hu, Shuo aut Chen, Xiang (orcid)0000-0001-8187-636X aut Peng, Cong (orcid)0000-0001-7104-5490 aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 41(2022), 1 vom: 13. Aug. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:41 year:2022 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13046-022-02427-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2022 1 13 08
allfields_unstemmed	10.1186/s13046-022-02427-w doi (DE-627)SPR050923277 (SPR)s13046-022-02427-w-e DE-627 ger DE-627 rakwb eng Zhang, Xu verfasserin aut CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. CD147, Keratinocyte, Malignant transformation, RSK2 (dpeaa)DE-He213 Guo, Yeye aut Xiao, Ta aut Li, Jie aut Guo, Aiyuan aut Lei, Li aut Jin, Chong aut Long, Qi aut Su, Juan aut Yin, Mingzhu aut Liu, Hong aut Chen, Chao aut Zhou, Zhe aut Zhu, Susi aut Tao, Juan aut Hu, Shuo aut Chen, Xiang (orcid)0000-0001-8187-636X aut Peng, Cong (orcid)0000-0001-7104-5490 aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 41(2022), 1 vom: 13. Aug. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:41 year:2022 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13046-022-02427-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2022 1 13 08
allfieldsGer	10.1186/s13046-022-02427-w doi (DE-627)SPR050923277 (SPR)s13046-022-02427-w-e DE-627 ger DE-627 rakwb eng Zhang, Xu verfasserin aut CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. CD147, Keratinocyte, Malignant transformation, RSK2 (dpeaa)DE-He213 Guo, Yeye aut Xiao, Ta aut Li, Jie aut Guo, Aiyuan aut Lei, Li aut Jin, Chong aut Long, Qi aut Su, Juan aut Yin, Mingzhu aut Liu, Hong aut Chen, Chao aut Zhou, Zhe aut Zhu, Susi aut Tao, Juan aut Hu, Shuo aut Chen, Xiang (orcid)0000-0001-8187-636X aut Peng, Cong (orcid)0000-0001-7104-5490 aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 41(2022), 1 vom: 13. Aug. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:41 year:2022 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13046-022-02427-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2022 1 13 08
allfieldsSound	10.1186/s13046-022-02427-w doi (DE-627)SPR050923277 (SPR)s13046-022-02427-w-e DE-627 ger DE-627 rakwb eng Zhang, Xu verfasserin aut CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. CD147, Keratinocyte, Malignant transformation, RSK2 (dpeaa)DE-He213 Guo, Yeye aut Xiao, Ta aut Li, Jie aut Guo, Aiyuan aut Lei, Li aut Jin, Chong aut Long, Qi aut Su, Juan aut Yin, Mingzhu aut Liu, Hong aut Chen, Chao aut Zhou, Zhe aut Zhu, Susi aut Tao, Juan aut Hu, Shuo aut Chen, Xiang (orcid)0000-0001-8187-636X aut Peng, Cong (orcid)0000-0001-7104-5490 aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 41(2022), 1 vom: 13. Aug. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:41 year:2022 number:1 day:13 month:08 https://dx.doi.org/10.1186/s13046-022-02427-w kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 41 2022 1 13 08
language	English
source	Enthalten in Journal of experimental & clinical cancer research 41(2022), 1 vom: 13. Aug. volume:41 year:2022 number:1 day:13 month:08
sourceStr	Enthalten in Journal of experimental & clinical cancer research 41(2022), 1 vom: 13. Aug. volume:41 year:2022 number:1 day:13 month:08
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	CD147, Keratinocyte, Malignant transformation, RSK2
isfreeaccess_bool	true
container_title	Journal of experimental & clinical cancer research
authorswithroles_txt_mv	Zhang, Xu @@aut@@ Guo, Yeye @@aut@@ Xiao, Ta @@aut@@ Li, Jie @@aut@@ Guo, Aiyuan @@aut@@ Lei, Li @@aut@@ Jin, Chong @@aut@@ Long, Qi @@aut@@ Su, Juan @@aut@@ Yin, Mingzhu @@aut@@ Liu, Hong @@aut@@ Chen, Chao @@aut@@ Zhou, Zhe @@aut@@ Zhu, Susi @@aut@@ Tao, Juan @@aut@@ Hu, Shuo @@aut@@ Chen, Xiang @@aut@@ Peng, Cong @@aut@@
publishDateDaySort_date	2022-08-13T00:00:00Z
hierarchy_top_id	568921380
id	SPR050923277
language_de	englisch
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Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. 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author	Zhang, Xu
spellingShingle	Zhang, Xu misc CD147, Keratinocyte, Malignant transformation, RSK2 CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
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topic_title	CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway CD147, Keratinocyte, Malignant transformation, RSK2 (dpeaa)DE-He213
topic	misc CD147, Keratinocyte, Malignant transformation, RSK2
topic_unstemmed	misc CD147, Keratinocyte, Malignant transformation, RSK2
topic_browse	misc CD147, Keratinocyte, Malignant transformation, RSK2
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title	CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
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title_full	CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
author_sort	Zhang, Xu
journal	Journal of experimental & clinical cancer research
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author_browse	Zhang, Xu Guo, Yeye Xiao, Ta Li, Jie Guo, Aiyuan Lei, Li Jin, Chong Long, Qi Su, Juan Yin, Mingzhu Liu, Hong Chen, Chao Zhou, Zhe Zhu, Susi Tao, Juan Hu, Shuo Chen, Xiang Peng, Cong
container_volume	41
format_se	Elektronische Aufsätze
author-letter	Zhang, Xu
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title_sort	cd147 mediates epidermal malignant transformation through the rsk2/ap-1 pathway
title_auth	CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
abstract	Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. © The Author(s) 2022
abstractGer	Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. © The Author(s) 2022
abstract_unstemmed	Background Malignant transformation of the epidermis is an essential process in the pathogenesis of cutaneous squamous-cell carcinoma (cSCC). Although evidence has demonstrated that CD147 plays key roles in various tumors, the role of CD147 in epidermal malignant transformation in vivo remains unclear. Methods Epidermal CD147-overexpression or knockout ($ Epi^{CD147-OE} $ or $ Epi^{CD147-KO} $) transgenic mouse models were generated for in vivo study. RNA-sequencing and q-PCR were performed to identify the differentially expressed genes. Immunohistochemistry and flow cytometry were performed to investigate the role of CD147 in regulating myeloid-derived suppressor cells (MDSCs). Immunoprecipitation, EMSA and ChIP assays were performed to investigate the mechanism of CD147 in cell transformation. Results We found that specific overexpression of CD147 in the epidermis ($ Epi^{CD147-OE} $) induces spontaneous tumor formation; moreover, a set of chemokines and cytokines including CXCL1, which play essential function in MDSC recruitment, were significantly upregulated in $ Epi^{CD147-OE} $ transgenic mice. As expected, overexpression of CD147 in the epidermis remarkably facilitated tumorigenesis by increasing the rate of tumor initiation and the number and size of tumors in the DMBA/TPA mouse model. Interestingly, the expression of CXCL1 and the infiltration of MDSCs were dramatically increased in $ Epi^{CD147-OE} $ transgenic mice. Our findings also showed that knockdown of CD147 attenuated EGF-induced malignant transformation as well as CXCL1 expression in HaCaT cells. Consistently, CD147 was found overexpressed in cutaneous squamous cell carcinoma (cSCC), and positively related with the expression of CD33, a myeloid-associated marker. We further identified RSK2, a serine/threonine kinase, as an interacting partner of CD147 at the binding site of $ CD147^{D207-230} $. The interaction of CD147 and RSK2 activated RSK2, thus enhancing AP-1 transcriptional activation. Furthermore, EMSAs and ChIP assays showed that AP-1 could associate with the CXCL1 promoter. Importantly, RSK2 inhibitor suppressed the tumor growth in DMBA/TPA mouse model by inhibiting the recruitment of MDSCs. Conclusion Our findings demonstrate that CD147 exerts a key function in epidermal malignant transformation in vivo by activating keratinocytes and recruiting MDSCs via the RSK2/AP-1 pathway. © The Author(s) 2022
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title_short	CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway
url	https://dx.doi.org/10.1186/s13046-022-02427-w
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author2	Guo, Yeye Xiao, Ta Li, Jie Guo, Aiyuan Lei, Li Jin, Chong Long, Qi Su, Juan Yin, Mingzhu Liu, Hong Chen, Chao Zhou, Zhe Zhu, Susi Tao, Juan Hu, Shuo Chen, Xiang Peng, Cong
author2Str	Guo, Yeye Xiao, Ta Li, Jie Guo, Aiyuan Lei, Li Jin, Chong Long, Qi Su, Juan Yin, Mingzhu Liu, Hong Chen, Chao Zhou, Zhe Zhu, Susi Tao, Juan Hu, Shuo Chen, Xiang Peng, Cong
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CD147 mediates epidermal malignant transformation through the RSK2/AP-1 pathway

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