School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines; Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
J Mol Med (Berl). 2023 Aug;101(8):917-929. doi: 10.1007/s00109-023-02337-0. Epub 2023 Jun 17.
Transcription factor EB, a member of the microphthalmia-associated transcription factor (MiTF/TFE) family, is a master regulator of autophagy, lysosome biogenesis, and TAMs. Metastasis is one of the main reasons for the failure of tumor therapy. Studies on the relationship between TFEB and tumor metastasis are contradictory. On the positive side, TFEB mainly affects tumor cell metastasis via five aspects, including autophagy, epithelial-mesenchymal transition (EMT), lysosomal biogenesis, lipid metabolism, and oncogenic signaling pathways; on the negative side, TFEB mainly affects tumor cell metastasis in two aspects, including tumor-associated macrophages (TAMs) and EMT. In this review, we described the detailed mechanism of TFEB-mediated regulation of metastasis. In addition, we also described the activation and inactivation of TFEB in several aspects, including the mTORC1 and Rag GTPase systems, ERK2, and AKT. However, the exact process by which TFEB regulates tumor metastasis remains unclear in some pathways, which requires further studies.
转录因子 EB（Transcription factor EB，TFEB）是微小脑畸形相关转录因子（Microphthalmia-associated transcription factor，MiTF/TFE）家族的成员，是自噬、溶酶体生物发生和 TAMs 的主要调节因子。转移是肿瘤治疗失败的主要原因之一。关于 TFEB 与肿瘤转移之间的关系的研究结果存在矛盾。从积极的方面来看，TFEB 主要通过五个方面影响肿瘤细胞的转移，包括自噬、上皮-间充质转化（epithelial-mesenchymal transition，EMT）、溶酶体生物发生、脂质代谢和致癌信号通路；从消极的方面来看，TFEB 主要通过两个方面影响肿瘤细胞的转移，包括肿瘤相关巨噬细胞（tumor-associated macrophages，TAMs）和 EMT。在这篇综述中，我们描述了 TFEB 介导的转移调节的详细机制。此外，我们还描述了 TFEB 在几个方面的激活和失活，包括 mTORC1 和 Rag GTPase 系统、ERK2 和 AKT。然而，TFEB 调节肿瘤转移的确切过程在某些途径中仍不清楚，这需要进一步的研究。
