Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network

Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expressi...
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Autor*in:	Zhang, Yanhao [verfasserIn] Jiang, Xiuxing Deng, Qin Gao, Ziyi Tang, Xiangyu Fu, Ruoqiu Hu, Jinjiao Li, Yunong Li, Lirong Gao, Ning

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	Autophagy/Mitophagy Cepharanthine (CEP) MYO1C F-actin Autophagosome-lysosome fusion

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Journal of experimental & clinical cancer research - Berlin : Springer, 2008, 38(2019), 1 vom: 07. Nov.
Übergeordnetes Werk:	volume:38 ; year:2019 ; number:1 ; day:07 ; month:11

Links:	Volltext

DOI / URN:	10.1186/s13046-019-1449-8

Katalog-ID:	SPR029649706

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520			\|a Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer.
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allfields	10.1186/s13046-019-1449-8 doi (DE-627)SPR029649706 (SPR)s13046-019-1449-8-e DE-627 ger DE-627 rakwb eng Zhang, Yanhao verfasserin aut Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. Autophagy/Mitophagy (dpeaa)DE-He213 Cepharanthine (CEP) (dpeaa)DE-He213 MYO1C (dpeaa)DE-He213 F-actin (dpeaa)DE-He213 Autophagosome-lysosome fusion (dpeaa)DE-He213 Jiang, Xiuxing aut Deng, Qin aut Gao, Ziyi aut Tang, Xiangyu aut Fu, Ruoqiu aut Hu, Jinjiao aut Li, Yunong aut Li, Lirong aut Gao, Ning aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 07. Nov. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:07 month:11 https://dx.doi.org/10.1186/s13046-019-1449-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 07 11
spelling	10.1186/s13046-019-1449-8 doi (DE-627)SPR029649706 (SPR)s13046-019-1449-8-e DE-627 ger DE-627 rakwb eng Zhang, Yanhao verfasserin aut Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. Autophagy/Mitophagy (dpeaa)DE-He213 Cepharanthine (CEP) (dpeaa)DE-He213 MYO1C (dpeaa)DE-He213 F-actin (dpeaa)DE-He213 Autophagosome-lysosome fusion (dpeaa)DE-He213 Jiang, Xiuxing aut Deng, Qin aut Gao, Ziyi aut Tang, Xiangyu aut Fu, Ruoqiu aut Hu, Jinjiao aut Li, Yunong aut Li, Lirong aut Gao, Ning aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 07. Nov. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:07 month:11 https://dx.doi.org/10.1186/s13046-019-1449-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 07 11
allfields_unstemmed	10.1186/s13046-019-1449-8 doi (DE-627)SPR029649706 (SPR)s13046-019-1449-8-e DE-627 ger DE-627 rakwb eng Zhang, Yanhao verfasserin aut Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. Autophagy/Mitophagy (dpeaa)DE-He213 Cepharanthine (CEP) (dpeaa)DE-He213 MYO1C (dpeaa)DE-He213 F-actin (dpeaa)DE-He213 Autophagosome-lysosome fusion (dpeaa)DE-He213 Jiang, Xiuxing aut Deng, Qin aut Gao, Ziyi aut Tang, Xiangyu aut Fu, Ruoqiu aut Hu, Jinjiao aut Li, Yunong aut Li, Lirong aut Gao, Ning aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 07. Nov. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:07 month:11 https://dx.doi.org/10.1186/s13046-019-1449-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 07 11
allfieldsGer	10.1186/s13046-019-1449-8 doi (DE-627)SPR029649706 (SPR)s13046-019-1449-8-e DE-627 ger DE-627 rakwb eng Zhang, Yanhao verfasserin aut Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. Autophagy/Mitophagy (dpeaa)DE-He213 Cepharanthine (CEP) (dpeaa)DE-He213 MYO1C (dpeaa)DE-He213 F-actin (dpeaa)DE-He213 Autophagosome-lysosome fusion (dpeaa)DE-He213 Jiang, Xiuxing aut Deng, Qin aut Gao, Ziyi aut Tang, Xiangyu aut Fu, Ruoqiu aut Hu, Jinjiao aut Li, Yunong aut Li, Lirong aut Gao, Ning aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 07. Nov. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:07 month:11 https://dx.doi.org/10.1186/s13046-019-1449-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 07 11
allfieldsSound	10.1186/s13046-019-1449-8 doi (DE-627)SPR029649706 (SPR)s13046-019-1449-8-e DE-627 ger DE-627 rakwb eng Zhang, Yanhao verfasserin aut Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. Autophagy/Mitophagy (dpeaa)DE-He213 Cepharanthine (CEP) (dpeaa)DE-He213 MYO1C (dpeaa)DE-He213 F-actin (dpeaa)DE-He213 Autophagosome-lysosome fusion (dpeaa)DE-He213 Jiang, Xiuxing aut Deng, Qin aut Gao, Ziyi aut Tang, Xiangyu aut Fu, Ruoqiu aut Hu, Jinjiao aut Li, Yunong aut Li, Lirong aut Gao, Ning aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 07. Nov. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:07 month:11 https://dx.doi.org/10.1186/s13046-019-1449-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER 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 07 11
language	English
source	Enthalten in Journal of experimental & clinical cancer research 38(2019), 1 vom: 07. Nov. volume:38 year:2019 number:1 day:07 month:11
sourceStr	Enthalten in Journal of experimental & clinical cancer research 38(2019), 1 vom: 07. Nov. volume:38 year:2019 number:1 day:07 month:11
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Autophagy/Mitophagy Cepharanthine (CEP) MYO1C F-actin Autophagosome-lysosome fusion
isfreeaccess_bool	true
container_title	Journal of experimental & clinical cancer research
authorswithroles_txt_mv	Zhang, Yanhao @@aut@@ Jiang, Xiuxing @@aut@@ Deng, Qin @@aut@@ Gao, Ziyi @@aut@@ Tang, Xiangyu @@aut@@ Fu, Ruoqiu @@aut@@ Hu, Jinjiao @@aut@@ Li, Yunong @@aut@@ Li, Lirong @@aut@@ Gao, Ning @@aut@@
publishDateDaySort_date	2019-11-07T00:00:00Z
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author	Zhang, Yanhao
spellingShingle	Zhang, Yanhao misc Autophagy/Mitophagy misc Cepharanthine (CEP) misc MYO1C misc F-actin misc Autophagosome-lysosome fusion Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network
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topic_title	Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network Autophagy/Mitophagy (dpeaa)DE-He213 Cepharanthine (CEP) (dpeaa)DE-He213 MYO1C (dpeaa)DE-He213 F-actin (dpeaa)DE-He213 Autophagosome-lysosome fusion (dpeaa)DE-He213
topic	misc Autophagy/Mitophagy misc Cepharanthine (CEP) misc MYO1C misc F-actin misc Autophagosome-lysosome fusion
topic_unstemmed	misc Autophagy/Mitophagy misc Cepharanthine (CEP) misc MYO1C misc F-actin misc Autophagosome-lysosome fusion
topic_browse	misc Autophagy/Mitophagy misc Cepharanthine (CEP) misc MYO1C misc F-actin misc Autophagosome-lysosome fusion
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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title	Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network
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title_full	Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network
author_sort	Zhang, Yanhao
journal	Journal of experimental & clinical cancer research
journalStr	Journal of experimental & clinical cancer research
lang_code	eng
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author_browse	Zhang, Yanhao Jiang, Xiuxing Deng, Qin Gao, Ziyi Tang, Xiangyu Fu, Ruoqiu Hu, Jinjiao Li, Yunong Li, Lirong Gao, Ning
container_volume	38
format_se	Elektronische Aufsätze
author-letter	Zhang, Yanhao
doi_str_mv	10.1186/s13046-019-1449-8
title_sort	downregulation of myo1c mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the f-actin network
title_auth	Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network
abstract	Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. © The Author(s). 2019
abstractGer	Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. © The Author(s). 2019
abstract_unstemmed	Background MYO1C, an actin-based motor protein, is involved in the late stages of autophagosome maturation and fusion with the lysosome. The molecular mechanism by which MYO1C regulates autophagosome-lysosome fusion remains largely unclear. Methods Western blotting was used to determine the expression of autophagy-related proteins. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes. An immunoprecipitation assay was utilized to detect protein-protein interactions. Immunofluorescence analysis was used to detect autophagosome-lysosome fusion and colocalization of autophagy-related molecules. An overexpression plasmid or siRNA against MYO1C were sequentially introduced into human breast cancer MDA-MB-231 cells. Results We show here that cepharanthine (CEP), a novel autophagy inhibitor, inhibited autophagy/mitophagy through blockage of autophagosome-lysosome fusion in human breast cancer cells. Mechanistically, we found for the first time that MYO1C was downregulated by CEP treatment. Furthermore, the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 was inhibited by CEP treatment. Knockdown of MYO1C further decreased the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment, leading to blockade of autophagosome-lysosome fusion. In contrast, overexpression of MYO1C significantly restored the interaction/colocalization of MYO1C and F-actin with either LC3 or LAMP1 inhibited by CEP treatment. Conclusion These findings highlight a key role of MYO1C in the regulation of autophagosome-lysosome fusion through F-actin remodeling. Our findings also suggest that CEP could potentially be further developed as a novel autophagy/mitophagy inhibitor, and a combination of CEP with classic chemotherapeutic drugs could become a promising treatment for breast cancer. © The Author(s). 2019
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container_issue	1
title_short	Downregulation of MYO1C mediated by cepharanthine inhibits autophagosome-lysosome fusion through blockade of the F-actin network
url	https://dx.doi.org/10.1186/s13046-019-1449-8
remote_bool	true
author2	Jiang, Xiuxing Deng, Qin Gao, Ziyi Tang, Xiangyu Fu, Ruoqiu Hu, Jinjiao Li, Yunong Li, Lirong Gao, Ning
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up_date	2024-07-04T01:51:55.345Z
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