Wanjun Tang, Karrie Mei Yee Kiang, Gilberto Ka Kit Leung
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引用次数: 0
Abstract
Chaperone-mediated autophagy (CMA) is a selective form of autophagy that targets proteins with the KFERQ-like motif for lysosomal degradation. This process involves the binding of substrate proteins to the chaperone HSC70 and their subsequent transport to the receptor LAMP2A on the lysosome membrane for degradation. Previous studies have shown a significant increase in the expression level of LAMP2A and the CMA activity in glioblastoma (GBM). However, the comprehensive role of CMA in GBM pathogenesis remains unclear. In this study, we observed a progressive elevation in LAMP2A expression with increasing GBM cell confluence. Notably, inhibition of CMA through LAMP2A knockdown markedly promoted GBM growth in orthotopic mouse models, accompanied by upregulation of positive cell cycle regulators. Conversely, overexpression of LAMP2A delayed GBM cell growth and increased sub-G1 cell percentages. Treatment with CMA activators induced cell death in GBM cells while preserving normal astrocyte viability at equivalent concentrations. Our results suggest that the upregulated expression of LAMP2A in GBM cells may be influenced by the tumor microenvironment rather than being a primary driver of GBM aggressiveness. Furthermore, activating CMA could serve as a potential therapeutic strategy to inhibit GBM growth while safeguarding normal cell viability.
Citation Format: Wanjun Tang, Karrie Mei Yee Kiang, Gilberto Ka Kit Leung. Enhancing chaperone-mediated autophagy to impede glioblastoma growth [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr A011.
期刊介绍:
Molecular Cancer Therapeutics will focus on basic research that has implications for cancer therapeutics in the following areas: Experimental Cancer Therapeutics, Identification of Molecular Targets, Targets for Chemoprevention, New Models, Cancer Chemistry and Drug Discovery, Molecular and Cellular Pharmacology, Molecular Classification of Tumors, and Bioinformatics and Computational Molecular Biology. The journal provides a publication forum for these emerging disciplines that is focused specifically on cancer research. Papers are stringently reviewed and only those that report results of novel, timely, and significant research and meet high standards of scientific merit will be accepted for publication.