Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma

Zhao-Xing Li; Ming-Chuang Sun; Kang Fang; Zi-Ying Zhao; Zhu-Yun Leng; Ze-Hua Zhang; Ai-Ping Xu; Yuan Chu; Li Zhang; Jingjing Lian; Tao Chen; Mei-Dong Xu

doi:10.1080/15384047.2023.2246206

Transcription factor 3 promotes migration and invasion potential and maintains cancer stemness by activating ID1 expression in esophageal squamous cell carcinoma

Cancer Biol Ther. 2023 Dec 31;24(1):2246206. doi: 10.1080/15384047.2023.2246206.

Authors

Affiliations

¹ Endoscopy Center, Department of Gastroenterology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Pathology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.

Abstract

Transcription factor 3 (TCF3) is a member of the basic Helix - Loop - Helix (bHLH) transcription factor (TF) family and is encoded by the TCF3 gene (also known as E2A). It has been shown that TCF3 functions as a key transcription factor in the pathogenesis of several human cancers and plays an important role in stem cell maintenance and carcinogenesis. However, the effect of TCF3 in the progression of esophageal squamous cell carcinoma (ESCC) is poorly known. In our study, TCF3 was found to express highly and correlated with cancer stage and prognosis. TCF3 was shown to promote ESCC invasion, migration, and drug resistance both from the results of in vivo and in vitro assays. Moreover, further studies suggested that TCF3 played these roles through transcriptionally regulating Inhibitor of DNA binding 1(ID1). Notably, we also found that TCF3 or ID1 was associated with ESCC stemness. Furthermore, TCF3 was correlated with the expression of cancer stemness markers CD44 and CD133. Therefore, maintaining cancer stemness might be the underlying mechanism that TCF3 transcriptionally regulated ID1 and further promoted ESCC progression and drug resistance.

Keywords: ID1; TCF3; cancer stem cell; cancer stemness; esophageal squamous cell carcinoma.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Basic Helix-Loop-Helix Transcription Factors
Carcinogenesis
Esophageal Neoplasms* / genetics
Esophageal Squamous Cell Carcinoma* / genetics
Humans
Inhibitor of Differentiation Protein 1 / genetics
Transcription Factor 3
Transcription Factors

Substances

Basic Helix-Loop-Helix Transcription Factors
ID1 protein, human
Inhibitor of Differentiation Protein 1
Transcription Factor 3
Transcription Factors
TCF3 protein, human

Grants and funding

This study was supported by grants from the National Natural Science Foundation of China (82072684 and 82073224), Shanghai Committee of Science and Technology (20XD1402900, 21XD1423100, 21JC1405200, and 18140900100), Medical Discipline Construction Project of Pudong Health Committee of Shanghai (PWZxq2022-6 and PWYgf2021-2), General projects of the Health Commission of Pudong New District (W2020A-40) and the Top- level Clinical Discipline Project of Shanghai Pudong (PWYgf2021-2).