The Role of Chaperone-Mediated Autophagy in Cell Cycle Control and Its Implications in Cancer

Author(s)

Andrade-Tomaz, Marina ^[1] ; de Souza, Izadora ^[1] ; Ribeiro Reily Rocha, Clarissa ^[1] ; Rodrigues Gomes, Luciana ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Dept Oncol Clin & Expt, Escola Paulista Med, BR-04037003 Sao Paulo, SP - Brazil

^[2] Inst Butantan, Ctr Toxins Immune Response & Cell Signaling CeTIC, Lab Ciclo Celular, BR-05503001 Sao Paulo, SP - Brazil

• Document type: Review article
• Source: CELLS; v. 9, n. 9 SEP 2020.
• Web of Science Citations: 0

Abstract

The cell cycle involves a network of proteins that modulate the sequence and timing of proliferation events. Unregulated proliferation is the most fundamental hallmark of cancer; thus, changes in cell cycle control are at the heart of malignant transformation processes. Several cellular processes can interfere with the cell cycle, including autophagy, the catabolic pathway involved in degradation of intracellular constituents in lysosomes. According to the mechanism used to deliver cargo to the lysosome, autophagy can be classified as macroautophagy (MA), microautophagy (MI), or chaperone-mediated autophagy (CMA). Distinct from other autophagy types, CMA substrates are selectively recognized by a cytosolic chaperone, one-by-one, and then addressed for degradation in lysosomes. The function of MA in cell cycle control, and its influence in cancer progression, are already well-established. However, regulation of the cell cycle by CMA, in the context of tumorigenesis, has not been fully addressed. This review aims to present and debate the molecular mechanisms by which CMA can interfere in the cell cycle, in the context of cancer. Thus, cell cycle modulators, such as MYC, hypoxia-inducible factor-1 subunit alpha (HIF-1 alpha), and checkpoint kinase 1 (CHK1), regulated by CMA activity will be discussed. Finally, the review will focus on how CMA dysfunction may impact the cell cycle, and as consequence promote tumorigenesis. (AU)

• FAPESP's process: 13/07467-1 - CeTICS - Center of Toxins, Immune-Response and Cell Signaling
• Grantee: Hugo Aguirre Armelin
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 19/21745-0 - Exploring drug resistance mechanisms in cancer cells via CRISPR libraries
• Grantee: Clarissa Ribeiro Reily Rocha
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/19435-3 - The role of DNA damage and mitochondrial function in vascular, immune and neurological ageing (DNA MoVINg)
• Grantee: Carlos Frederico Martins Menck
• Support Opportunities: Research Projects - Thematic Grants