Targeting CSC-related transcription factors by E3 ubiquitin ligases for cancer therapy.

Semin Cancer Biol

Department of Scientific Research Center, Zhejiang Zhongwei Medical Research Center, Hangzhou, Zhejiang 310018, China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, China; Department of Biochemistry, Bengbu Medical College, Bengbu, Anhui 233000, China. Electronic address:

Published: December 2022

Evidence has revealed that transcription factors play essential roles in regulation of multiple cellular processes, including cell proliferation, metastasis, EMT, cancer stem cells and chemoresistance. Dysregulated expression levels of transcription factors contribute to tumorigenesis and malignant progression. The expression of transcription factors is tightly governed by several signaling pathways, noncoding RNAs and E3 ubiquitin ligases. Cancer stem cells (CSCs) have been validated in regulation of tumor metastasis, reoccurrence and chemoresistance in human cancer. Transcription factors have been verified to participate in regulation of CSC formation, including Oct4, SOX2, KLF4, c-Myc, Nanog, GATA, SALL4, Bmi-1, OLIG2, POU3F2 and FOX proteins. In this review article, we will describe the critical role of CSC-related transcription factors. We will further discuss which E3 ligases regulate the degradation of these CSC-related transcription factors and their underlying mechanisms. We also mentioned the functions and mechanisms of EMT-associated transcription factors such as ZEB1, ZEB2, Snail, Slug, Twist1 and Twist2. Furthermore, we highlight the therapeutic potential via targeting E3 ubiquitin ligases for modulation of these transcription factors.

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http://dx.doi.org/10.1016/j.semcancer.2022.11.002DOI Listing

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