MiT/TFE 因子在癌症中的新兴作用。

Emerging roles of the MiT/TFE factors in cancer.

机构信息

Department of Molecular and Cellular Biology, University of California at Berkeley, Berkeley, CA 94720, USA.

Department of Anatomy, University of California San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94158, USA.

出版信息

Trends Cancer. 2023 Oct;9(10):817-827. doi: 10.1016/j.trecan.2023.06.005. Epub 2023 Jul 1.

DOI:10.1016/j.trecan.2023.06.005

PMID:37400313

Abstract

The microphthalmia/transcription factor E (MiT/TFE) transcription factors (TFs; TFEB, TFE3, MITF, and TFEC) play a central role in cellular catabolism and quality control and are subject to extensive layers of regulation that influence their localization, stability, and activity. Recent studies have highlighted a broader role for these TFs in driving diverse stress-adaptation pathways, which manifest in a context- and tissue-dependent manner. Several human cancers upregulate the MiT/TFE factors to survive extreme fluctuations in nutrients, energy, and pharmacological challenges. Emerging data suggest that reduced activity of the MiT/TFE factors can also promote tumorigenesis. Here, we outline recent findings relating to novel mechanisms of regulation and activity of MiT/TFE proteins across some of the most aggressive human cancers.

摘要

小眼畸形转录因子 E（MiT/TFE）转录因子（TFs；TFEB、TFE3、MITF 和 TFEC）在细胞分解代谢和质量控制中发挥核心作用，并且受到广泛的调控层的影响，这些调控层影响它们的定位、稳定性和活性。最近的研究强调了这些 TFs 在驱动多种应激适应途径中的更广泛作用，这些途径以组织和细胞环境依赖的方式表现出来。几种人类癌症上调 MiT/TFE 因子以在营养、能量和药物挑战的极端波动中存活。新出现的数据表明，MiT/TFE 因子活性降低也可促进肿瘤发生。在这里，我们概述了与一些最具侵袭性的人类癌症中 MiT/TFE 蛋白的新调节和活性机制相关的最新发现。