E26 transformation-specific transcription variant 5 in development and cancer: modification, regulation and function

Abstract

E26 transformation-specific (ETS) transcription variant 5 (ETV5), also known as ETS-related molecule (ERM), exerts versatile functions in normal physiological processes, including branching morphogenesis, neural system development, fertility, embryonic development, immune regulation, and cell metabolism. In addition, ETV5 is repeatedly found to be overexpressed in multiple malignant tumors, where it is involved in cancer progression as an oncogenic transcription factor. Its roles in cancer metastasis, proliferation, oxidative stress response and drug resistance indicate that it is a potential prognostic biomarker, as well as a therapeutic target for cancer treatment. Post-translational modifications, gene fusion events, sophisticated cellular signaling crosstalk and non-coding RNAs contribute to the dysregulation and abnormal activities of ETV5. However, few studies to date systematically summarized the role and molecular mechanisms of ETV5 in benign diseases and in oncogenic progression. In this review, we specify the molecular structure and post-translational modifications of ETV5. In addition, its critical roles in benign and malignant diseases are summarized to draw a panorama for specialists and clinicians. The updated molecular mechanisms of ETV5 in cancer biology and tumor progression are delineated. Finally, we prospect the further direction of ETV5 research in oncology and its potential translational applications in the clinic.

YTHDF2 Is a Therapeutic Target for HCC by Suppressing Immune Evasion and Angiogenesis Through ETV5/PD‐L1/VEGFA Axis

“…[23,24] Dysregulation of TFs plays an essential role in regulating tumor microenvironment (TME) and subsequently impacts tumorigenesis. [25][26][27] Currently, the impact of m 6 A modification and m 6 A regulators on immune evasion and angiogenesis through the regulation of TFs remain unclear. Exploring the m 6 A modification on TFs may disclose new molecular mechanisms of HCC pathology and inspire promising therapeutic strategies for HCC treatment.…”

ETV7 promotes colorectal cancer progression through upregulation of IFIT3

“…Members of the E26 transformation-specific (ETS) gene family regulate a series of genes participating in various processes related to cancer, including cell amplification, migration, cell cycle regulation, and angiogenesis (De Braekeleer et al 2012 ; Jiang et al 2021 ; Wei et al 2023 ). ETS variant transcription factor 7 (ETV7), also termed TEL2 or TELB, is a member of the ETS family.…”