Chaperone-mediated autophagy affects tumor cell proliferation and cisplatin resistance in esophageal squamous cell carcinoma.


Cao D(1), Shan D(1), Yan W(1), Zhang Z(1), Song Q(1), Jiang Y(1), Zhang X(1), Zhang Z(1), Wang Z(1), Wang Y(1)(2), Lu S(1).
Author information:
(1)National Center for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, School of Basic Medical Sciences, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
(2)Centre for Biomarkers & Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.


BACKGROUND: Chaperone-mediated autophagy (CMA) is a lysosomal degradation pathway of selective soluble proteins. Lysosomal membrane associated protein 2a (LAMP2a) is the lysosomal membrane receptor of CMA and influences CMA activity. Although it has been suggested that higher expression of LAMP2a is associated with more advanced tumor node metastasis (TNM) stages and shorter survival time in patients with esophageal squamous cell carcinoma (ESCC), the underlying mechanism has not been known yet. METHODS: In this study, we modulated the activity of CMA through LAMP2a or small molecular compounds in human ESCC cells to investigate its role in ESCC. RESULTS: We found that down-regulating the activity of CMA could inhibit the proliferation and colony formation of ESCC cells as well as increase their sensitivity to cisplatin. CONCLUSIONS: Our results promote better understanding of how CMA affects human ESCC and provide a new therapeutic target against ESCC through down-regulating LAMP2a.