Rios Javiera, Sequeida Alvaro, Albornoz Amelina, Budini Mauricio
Molecular and Cellular Pathology Laboratory, Dentistry Faculty, Institute in Dentistry Sciences, University of Chile, Santiago, Chile.
Fundación Ciencia & Vida, Santiago, Chile.
Front Oncol. 2021 Feb 12;10:614677. doi: 10.3389/fonc.2020.614677. eCollection 2020.
Chaperone-mediated autophagy (CMA) represents a specific way of lysosomal protein degradation and contrary to macro and microautophagy is independent of vesicles formation. The role of CMA in different physiopathological processes has been studied for several years. In cancer, alterations of the CMA principal components, Hsc70 and Lamp2A protein and mRNA levels, have been described in malignant cells. However, changes in the expression levels of these CMA components are not always associated with changes in CMA activity and their biological significance must be carefully interpreted case by case. The objective of this review is to discuss whether altering the CMA activity, CMA substrates or CMA components is accurate to avoid cancer progression. In particular, this review will discuss about the evidences in which alterations CMA components Lamp2A and Hsc70 are associated or not with changes in CMA activity in different cancer types. This analysis will help to better understand the role of CMA activity in cancer and to elucidate whether CMA can be considered as target for therapeutics. Further, it will help to define whether the attention of the investigation should be focused on Lamp2A and Hsc70 because they can have an independent role in cancer progression beyond of their participation in altered CMA activity.
伴侣介导的自噬（CMA）是溶酶体蛋白降解的一种特定方式，与巨自噬和微自噬不同，它不依赖于囊泡形成。多年来，人们一直在研究CMA在不同生理病理过程中的作用。在癌症中，已在恶性细胞中描述了CMA主要成分Hsc70和Lamp2A蛋白及mRNA水平的改变。然而，这些CMA成分表达水平的变化并不总是与CMA活性的变化相关，其生物学意义必须逐例仔细解读。本综述的目的是讨论改变CMA活性、CMA底物或CMA成分是否准确地避免癌症进展。特别是，本综述将讨论不同癌症类型中CMA成分Lamp2A和Hsc70的改变与CMA活性变化相关或不相关的证据。这一分析将有助于更好地理解CMA活性在癌症中的作用，并阐明CMA是否可被视为治疗靶点。此外，这将有助于确定研究是否应聚焦于Lamp2A和Hsc70，因为它们在癌症进展中可能除了参与改变的CMA活性外还具有独立作用。
