2. Academic Validation
  3. ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction

ANXA6 suppresses the tumorigenesis of cervical cancer through autophagy induction

  • Clin Transl Med. 2020 Oct;10(6):e208. doi: 10.1002/ctm2.208.
Xin Sun 1,  Yuhan Shu 2,  Mengting Xu 2,  Jiukun Jiang 3,  Liming Wang 4,  Jigang Wang 5 6 7,  Dongsheng Huang 8,  Jianbin Zhang 8
Affiliations

Affiliations

  • 1 Department of Oncology, People's Hospital of Hangzhou Medical College, Hangzhou, China.
  • 2 College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, China.
  • 3 Department of Emergency Medicine, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
  • 4 Department of Physiology, National University of Singapore, Singapore, Singapore.
  • 5 Artemisinin Research Center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
  • 6 The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
  • 7 Department of Toxicology, School of Public Health, Guangxi Medical University, Nanning, China.
  • 8 Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, People's Hospital of Hangzhou Medical College, Clinical Research Institute, Hangzhou, China.
PMID: 33135350 DOI: 10.1002/ctm2.208
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.

Keywords

ANXA6; ATG9A; ERK; autophagy; cervical cancer; mTOR.

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