Autophagy is a conserved "self-eating" recycling process which removes aggregated or misfolded proteins, or defective organelles, to maintain cellular hemostasis. In the autophagy-lysosome pathway (ALP), clearance of unwanted debris and materials occurs through the generation of the autophagosome, a complex of double-membrane bounded vesicles that form around cytosolic cargos and catabolize their contents by fusion to lysosomes. In tumors, autophagy has dichotomous functions via preventing tumor initiation but promoting tumor progression. The basic helix-loop-helix leucine zipper transcription factor EB (TFEB) activates the promoters of genes encoding for proteins, which participate in this cellular degradative system by regulating lysosomal biogenesis, lysosomal acidification, lysosomal exocytosis and autophagy. In humans, disturbances of ALP are related to various pathological conditions. Recently, TFEB dysregulation was found to have a crucial pathogenic role in different tumors by modulating tumor cell autophagy. Notably, in renal cell carcinomas, different TFEB gene fusions were reported to promote oncogenic features. In this review, we discuss the role of TFEB in human cancers with a special focus on potential diagnostic and therapeutic implications.

中文翻译：

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TFEB在肿瘤细胞自噬中的作用：诊断和治疗机会。

自噬是一种保守的“自食”循环过程，可去除聚集或错误折叠的蛋白质或有缺陷的细胞器，以维持细胞止血。在自噬-溶酶体途径（ALP）中，不需要的碎片和物质的清除通过自噬体的产生而发生，自噬体是在细胞质货物周围形成并通过与溶酶体融合而分解其内容物的双膜结合囊泡的复合物。在肿瘤中，自噬通过阻止肿瘤的发生但促进肿瘤的发展而具有二分功能。基本的螺旋-环-螺旋亮氨酸拉链转录因子EB（TFEB）激活编码蛋白质的基因的启动子，这些蛋白质通过调节溶酶体生物发生，溶酶体酸化，溶酶体胞吐作用和自噬而参与该细胞降解系统。在人类中 ALP的紊乱与各种病理状况有关。最近，通过调节肿瘤细胞自噬，发现TFEB失调在不同肿瘤中具有关键的致病作用。值得注意的是，在肾细胞癌中，据报道不同的TFEB基因融合可促进致癌性。在这篇综述中，我们讨论了TFEB在人类癌症中的作用，并特别关注潜在的诊断和治疗意义。