Cellular Oncology Group, Biodonostia Health Research Institute, San Sebastian, Spain.
CIBER de Fragilidad y Envejecimiento Saludable (CIBERfes), Madrid, Spain.
Autophagy. 2022 Dec;18(12):3035-3036. doi: 10.1080/15548627.2022.2069450. Epub 2022 Apr 27.
Chaperone-mediated autophagy (CMA) is a selective type of autophagy specialized in the individual degradation of targeted proteins. Its impact in any cancer stem cell (CSC) subtype remained elusive. In a recent study, we characterized the expression of LAMP2A and CMA activity in glioblastoma revealing its enrichment in a glioma stem cell (GSC) subpopulation. LAMP2A downregulation diminishes proliferation and self-renewal and induces apoptosis in GSCs , whereas it delays tumor progression . The underlying molecular signature of CMA comprises several proteomic and transcriptomic pathways with special relevance to mitochondrial function, the interferon pathway and extracellular matrix interactions. Remarkably, these activities are translated into the clinical scenario, as glioblastoma (GBM) samples show increased expression of compared to healthy tissue, with this expression being positively associated with malignancy grade, TMZ resistance and lower patient survival. These results reveal a novel function of CMA as an intrinsic regulator of GSC tumorigenic properties and highlight its relevance in GBM progression.
伴侣蛋白介导的自噬（CMA）是一种选择性的自噬类型，专门用于靶向蛋白的个体降解。其在任何癌症干细胞（CSC）亚型中的作用仍不清楚。在最近的一项研究中，我们研究了脑胶质瘤中 LAMP2A 的表达和 CMA 活性，发现其在神经胶质瘤干细胞（GSC）亚群中富集。LAMP2A 的下调会减少 GSCs 的增殖和自我更新，并诱导其凋亡，而延迟肿瘤的进展。CMA 的潜在分子特征包括几个蛋白质组学和转录组学途径，这些途径与线粒体功能、干扰素途径和细胞外基质相互作用特别相关。值得注意的是，这些活性在临床情况下得到了转化，因为脑胶质瘤（GBM）样本与健康组织相比表现出更高的表达水平，这种表达与恶性程度、TMZ 耐药性和患者生存率降低呈正相关。这些结果揭示了 CMA 作为 GSC 肿瘤发生特性内在调节剂的新功能，并强调了其在 GBM 进展中的相关性。
