Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance
Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote can...
Ausführliche Beschreibung
Autor*in: |
Yingqiu Xie [verfasserIn] Ayan A. Nurkesh [verfasserIn] Nazgul Ibragimova [verfasserIn] Zhuldyz Zhanzak [verfasserIn] Aizhan Meyerbekova [verfasserIn] Zhanna Alexeyeva [verfasserIn] Aiya Yesbolatova [verfasserIn] Madina Satayeva [verfasserIn] Aidana Mustafa [verfasserIn] Limara Manarbek [verfasserIn] Aisulu Maipas [verfasserIn] Akerke Altaikyzy [verfasserIn] Zhibek Keneskhanova [verfasserIn] Burkitkan Akbay [verfasserIn] Zhenbang Chen [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2019 |
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Übergeordnetes Werk: |
In: Journal of Experimental & Clinical Cancer Research - BMC, 2008, 38(2019), 1, Seite 12 |
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Übergeordnetes Werk: |
volume:38 ; year:2019 ; number:1 ; pages:12 |
Links: |
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DOI / URN: |
10.1186/s13046-018-1004-z |
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Katalog-ID: |
DOAJ041557913 |
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520 | |a Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. | ||
650 | 4 | |a Nuclear localized membrane protein (NLMP) | |
650 | 4 | |a MET | |
650 | 4 | |a Cell death | |
650 | 4 | |a Drug resistance | |
650 | 4 | |a Cancer evolution | |
653 | 0 | |a Neoplasms. Tumors. Oncology. Including cancer and carcinogens | |
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10.1186/s13046-018-1004-z doi (DE-627)DOAJ041557913 (DE-599)DOAJ3e07a36b125a4e7e9c3679bfba543c7f DE-627 ger DE-627 rakwb eng RC254-282 Yingqiu Xie verfasserin aut Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. Nuclear localized membrane protein (NLMP) MET Cell death Drug resistance Cancer evolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ayan A. Nurkesh verfasserin aut Nazgul Ibragimova verfasserin aut Zhuldyz Zhanzak verfasserin aut Aizhan Meyerbekova verfasserin aut Zhanna Alexeyeva verfasserin aut Aiya Yesbolatova verfasserin aut Madina Satayeva verfasserin aut Aidana Mustafa verfasserin aut Limara Manarbek verfasserin aut Aisulu Maipas verfasserin aut Akerke Altaikyzy verfasserin aut Zhibek Keneskhanova verfasserin aut Burkitkan Akbay verfasserin aut Zhenbang Chen verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 38(2019), 1, Seite 12 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:38 year:2019 number:1 pages:12 https://doi.org/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/article/3e07a36b125a4e7e9c3679bfba543c7f kostenfrei http://link.springer.com/article/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 38 2019 1 12 |
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10.1186/s13046-018-1004-z doi (DE-627)DOAJ041557913 (DE-599)DOAJ3e07a36b125a4e7e9c3679bfba543c7f DE-627 ger DE-627 rakwb eng RC254-282 Yingqiu Xie verfasserin aut Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. Nuclear localized membrane protein (NLMP) MET Cell death Drug resistance Cancer evolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ayan A. Nurkesh verfasserin aut Nazgul Ibragimova verfasserin aut Zhuldyz Zhanzak verfasserin aut Aizhan Meyerbekova verfasserin aut Zhanna Alexeyeva verfasserin aut Aiya Yesbolatova verfasserin aut Madina Satayeva verfasserin aut Aidana Mustafa verfasserin aut Limara Manarbek verfasserin aut Aisulu Maipas verfasserin aut Akerke Altaikyzy verfasserin aut Zhibek Keneskhanova verfasserin aut Burkitkan Akbay verfasserin aut Zhenbang Chen verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 38(2019), 1, Seite 12 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:38 year:2019 number:1 pages:12 https://doi.org/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/article/3e07a36b125a4e7e9c3679bfba543c7f kostenfrei http://link.springer.com/article/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 38 2019 1 12 |
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10.1186/s13046-018-1004-z doi (DE-627)DOAJ041557913 (DE-599)DOAJ3e07a36b125a4e7e9c3679bfba543c7f DE-627 ger DE-627 rakwb eng RC254-282 Yingqiu Xie verfasserin aut Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. Nuclear localized membrane protein (NLMP) MET Cell death Drug resistance Cancer evolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ayan A. Nurkesh verfasserin aut Nazgul Ibragimova verfasserin aut Zhuldyz Zhanzak verfasserin aut Aizhan Meyerbekova verfasserin aut Zhanna Alexeyeva verfasserin aut Aiya Yesbolatova verfasserin aut Madina Satayeva verfasserin aut Aidana Mustafa verfasserin aut Limara Manarbek verfasserin aut Aisulu Maipas verfasserin aut Akerke Altaikyzy verfasserin aut Zhibek Keneskhanova verfasserin aut Burkitkan Akbay verfasserin aut Zhenbang Chen verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 38(2019), 1, Seite 12 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:38 year:2019 number:1 pages:12 https://doi.org/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/article/3e07a36b125a4e7e9c3679bfba543c7f kostenfrei http://link.springer.com/article/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 38 2019 1 12 |
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10.1186/s13046-018-1004-z doi (DE-627)DOAJ041557913 (DE-599)DOAJ3e07a36b125a4e7e9c3679bfba543c7f DE-627 ger DE-627 rakwb eng RC254-282 Yingqiu Xie verfasserin aut Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. Nuclear localized membrane protein (NLMP) MET Cell death Drug resistance Cancer evolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ayan A. Nurkesh verfasserin aut Nazgul Ibragimova verfasserin aut Zhuldyz Zhanzak verfasserin aut Aizhan Meyerbekova verfasserin aut Zhanna Alexeyeva verfasserin aut Aiya Yesbolatova verfasserin aut Madina Satayeva verfasserin aut Aidana Mustafa verfasserin aut Limara Manarbek verfasserin aut Aisulu Maipas verfasserin aut Akerke Altaikyzy verfasserin aut Zhibek Keneskhanova verfasserin aut Burkitkan Akbay verfasserin aut Zhenbang Chen verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 38(2019), 1, Seite 12 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:38 year:2019 number:1 pages:12 https://doi.org/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/article/3e07a36b125a4e7e9c3679bfba543c7f kostenfrei http://link.springer.com/article/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 38 2019 1 12 |
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10.1186/s13046-018-1004-z doi (DE-627)DOAJ041557913 (DE-599)DOAJ3e07a36b125a4e7e9c3679bfba543c7f DE-627 ger DE-627 rakwb eng RC254-282 Yingqiu Xie verfasserin aut Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. Nuclear localized membrane protein (NLMP) MET Cell death Drug resistance Cancer evolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens Ayan A. Nurkesh verfasserin aut Nazgul Ibragimova verfasserin aut Zhuldyz Zhanzak verfasserin aut Aizhan Meyerbekova verfasserin aut Zhanna Alexeyeva verfasserin aut Aiya Yesbolatova verfasserin aut Madina Satayeva verfasserin aut Aidana Mustafa verfasserin aut Limara Manarbek verfasserin aut Aisulu Maipas verfasserin aut Akerke Altaikyzy verfasserin aut Zhibek Keneskhanova verfasserin aut Burkitkan Akbay verfasserin aut Zhenbang Chen verfasserin aut In Journal of Experimental & Clinical Cancer Research BMC, 2008 38(2019), 1, Seite 12 (DE-627)568921380 (DE-600)2430698-8 17569966 nnns volume:38 year:2019 number:1 pages:12 https://doi.org/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/article/3e07a36b125a4e7e9c3679bfba543c7f kostenfrei http://link.springer.com/article/10.1186/s13046-018-1004-z kostenfrei https://doaj.org/toc/1756-9966 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA 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 38 2019 1 12 |
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Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance |
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Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance |
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Yingqiu Xie |
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Journal of Experimental & Clinical Cancer Research |
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Journal of Experimental & Clinical Cancer Research |
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Yingqiu Xie Ayan A. Nurkesh Nazgul Ibragimova Zhuldyz Zhanzak Aizhan Meyerbekova Zhanna Alexeyeva Aiya Yesbolatova Madina Satayeva Aidana Mustafa Limara Manarbek Aisulu Maipas Akerke Altaikyzy Zhibek Keneskhanova Burkitkan Akbay Zhenbang Chen |
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10.1186/s13046-018-1004-z |
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systematic analysis of nlmp suggests nuclear localization of rtk/met kinases resemble cancer cell clearance |
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Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance |
abstract |
Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. |
abstractGer |
Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. |
abstract_unstemmed |
Abstract Background Some membrane proteins can translocate into the nucleus, defined as nuclear localized membrane proteins (NLMPs), including receptor tyrosine kinases (RTKs). We previously showed that nuclear MET (nMET), a member of RTKs, mediates cancer stem-like cells self-renewal to promote cancer recurrence. However, it is unknown that nMET or mMET, which is the ancestor in the evolution of cancer cell survival and clearance. Here, we aim to study the NLMP functions in cell death, differentiation and survival. Method We applied the systematic reanalysis of functional NLMP and clinical investigations of nMET from databases. In addition, we used soft agar assay, immunoblotting, flow cytometry, and immunofluorescence confocal microscopy for examinations of nMET functions including stem-like cell formation, cell signaling, cell cycle regulation, and co-localization with regulators of cell signaling. ShRNA, antibody of recognizing surface membrane MET based treatment were used to downregulate endogenous nMET to uncover its function. Results We predicted and demonstrated that nMET and nEGFR are most likely not ancestors. nMET overexpression induces both cell death and survival with drug resistance and stem cell-like characters. Moreover, the paradoxical function of nMET in both cell death and cell survival is explained by the fact that nMET induces stem cell-like cell growth, DNA damage repair, to evade the drug sensitization for survival of single cells while non-stem cell-like nMET expressing single cells may undergo clearance by cell death through cell cycle arrest induced by p21. Conclusion Taken together, our data suggest a link between nuclear RTK and cancer cell evolutionary clearance via cell death, and drug resistance for survival through stemness selection. Targeting evolved nuclear RTKs in cancer stem cells would be a novel avenue for precision cancer therapy. |
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Systematic analysis of NLMP suggests nuclear localization of RTK/MET kinases resemble cancer cell clearance |
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https://doi.org/10.1186/s13046-018-1004-z https://doaj.org/article/3e07a36b125a4e7e9c3679bfba543c7f http://link.springer.com/article/10.1186/s13046-018-1004-z https://doaj.org/toc/1756-9966 |
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Ayan A. Nurkesh Nazgul Ibragimova Zhuldyz Zhanzak Aizhan Meyerbekova Zhanna Alexeyeva Aiya Yesbolatova Madina Satayeva Aidana Mustafa Limara Manarbek Aisulu Maipas Akerke Altaikyzy Zhibek Keneskhanova Burkitkan Akbay Zhenbang Chen |
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Ayan A. Nurkesh Nazgul Ibragimova Zhuldyz Zhanzak Aizhan Meyerbekova Zhanna Alexeyeva Aiya Yesbolatova Madina Satayeva Aidana Mustafa Limara Manarbek Aisulu Maipas Akerke Altaikyzy Zhibek Keneskhanova Burkitkan Akbay Zhenbang Chen |
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