ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction
Abstract Background Autophagy is an intracellular degradation pathway conserved in eukaryotes. ANXA6 (annexin A6) belongs to a family of calcium‐dependent membrane and phospholipid‐binding proteins. Here, we identify ANXA6 as a newly synthesized protein in starvation‐induced autophagy and validate i...
| Main Authors: | , , , , , , , |
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| Format: | Article |
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Wiley
2020-10-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.208 |
| _version_ | 1818655936177242112 |
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| author | Xin Sun Yuhan Shu Mengting Xu Jiukun Jiang Liming Wang Jigang Wang Dongsheng Huang Jianbin Zhang |
| author_facet | Xin Sun Yuhan Shu Mengting Xu Jiukun Jiang Liming Wang Jigang Wang Dongsheng Huang Jianbin Zhang |
| author_sort | Xin Sun |
| collection | DOAJ |
| description | Abstract Background Autophagy is an intracellular degradation pathway conserved in eukaryotes. ANXA6 (annexin A6) belongs to a family of calcium‐dependent membrane and phospholipid‐binding proteins. Here, we identify ANXA6 as a newly synthesized protein in starvation‐induced autophagy and validate it as a novel autophagy modulator that regulates autophagosome formation. Results ANXA6 knockdown attenuates starvation‐induced autophagy, while restoration of its expression enhances autophagy. GO (gene ontology) analysis of ANXA6 targets showed that ANXA6 interacts with many RAB GTPases and targets endocytosis and phagocytosis pathways, indicating that ANXA6 exerts its function through protein trafficking. ATG9A (autophagy‐related 9A) is the sole multispanning transmembrane protein and its trafficking through recycling endosomes is an essential step for autophagosome formation. Our results showed that ANXA6 enables appropriate ATG9A+ vesicle trafficking from endosomes to autophagosomes through RAB proteins or F‐actin. In addition, restoration of ANXA6 expression suppresses mTOR (mammalian target of rapamycin) activity through the inhibition of the PI3K (phosphoinositide 3‐kinase)‐AKT and ERK (extracellular signal‐regulated kinase) signaling pathways, which is a negative regulator of autophagy. Functionally, ANXA6 expression is correlated with LC3 (microtubule‐associated protein 1 light chain 3) expression in cervical cancer, and ANXA6 inhibits tumorigenesis through autophagy induction. Conclusions Our results reveal an important mechanism for ANXA6 in tumor suppression and autophagy regulation. |
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| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-17T03:17:36Z |
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| spelling | doaj.art-e8d9ce6fe4414d7ea57cb3f5670645822022-12-21T22:05:37ZengWileyClinical and Translational Medicine2001-13262020-10-01106n/an/a10.1002/ctm2.208ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy inductionXin Sun0Yuhan Shu1Mengting Xu2Jiukun Jiang3Liming Wang4Jigang Wang5Dongsheng Huang6Jianbin Zhang7Department of Oncology People's Hospital of Hangzhou Medical College Hangzhou ChinaCollege of Biomedical Engineering & Instrument Science Zhejiang University Hangzhou ChinaCollege of Biomedical Engineering & Instrument Science Zhejiang University Hangzhou ChinaDepartment of Emergency Medicine The First Affiliated Hospital School of Medicine Zhejiang University Hangzhou ChinaDepartment of Physiology National University of Singapore Singapore SingaporeArtemisinin Research Center, and Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing ChinaKey Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province People's Hospital of Hangzhou Medical College Clinical Research Institute Hangzhou ChinaKey Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province People's Hospital of Hangzhou Medical College Clinical Research Institute Hangzhou ChinaAbstract Background Autophagy is an intracellular degradation pathway conserved in eukaryotes. ANXA6 (annexin A6) belongs to a family of calcium‐dependent membrane and phospholipid‐binding proteins. Here, we identify ANXA6 as a newly synthesized protein in starvation‐induced autophagy and validate it as a novel autophagy modulator that regulates autophagosome formation. Results ANXA6 knockdown attenuates starvation‐induced autophagy, while restoration of its expression enhances autophagy. GO (gene ontology) analysis of ANXA6 targets showed that ANXA6 interacts with many RAB GTPases and targets endocytosis and phagocytosis pathways, indicating that ANXA6 exerts its function through protein trafficking. ATG9A (autophagy‐related 9A) is the sole multispanning transmembrane protein and its trafficking through recycling endosomes is an essential step for autophagosome formation. Our results showed that ANXA6 enables appropriate ATG9A+ vesicle trafficking from endosomes to autophagosomes through RAB proteins or F‐actin. In addition, restoration of ANXA6 expression suppresses mTOR (mammalian target of rapamycin) activity through the inhibition of the PI3K (phosphoinositide 3‐kinase)‐AKT and ERK (extracellular signal‐regulated kinase) signaling pathways, which is a negative regulator of autophagy. Functionally, ANXA6 expression is correlated with LC3 (microtubule‐associated protein 1 light chain 3) expression in cervical cancer, and ANXA6 inhibits tumorigenesis through autophagy induction. Conclusions Our results reveal an important mechanism for ANXA6 in tumor suppression and autophagy regulation.https://doi.org/10.1002/ctm2.208ANXA6ATG9Aautophagycervical cancerERKmTOR |
| spellingShingle | Xin Sun Yuhan Shu Mengting Xu Jiukun Jiang Liming Wang Jigang Wang Dongsheng Huang Jianbin Zhang ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction Clinical and Translational Medicine ANXA6 ATG9A autophagy cervical cancer ERK mTOR |
| title | ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction |
| title_full | ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction |
| title_fullStr | ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction |
| title_full_unstemmed | ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction |
| title_short | ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction |
| title_sort | anxa6 suppresses the tumorigenesis of cervical cancer through autophagy induction |
| topic | ANXA6 ATG9A autophagy cervical cancer ERK mTOR |
| url | https://doi.org/10.1002/ctm2.208 |
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