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

Thorac Cancer. 2021 Apr;12(7):1048-1057. doi: 10.1111/1759-7714.13849. Epub 2021 Feb 10.

Abstract

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.

Keywords: cell proliferation; chaperone-mediated autophagy; cisplatin resistance; esophageal squamous cell carcinoma; lysosomal membrane associated protein 2a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Chaperone-Mediated Autophagy / genetics*
  • Drug Resistance, Neoplasm / genetics*
  • Esophageal Squamous Cell Carcinoma / drug therapy*
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Signal Transduction
  • Transfection
  • Xenograft Model Antitumor Assays