Functional characterization of SOX2 as an anticancer target
Open Access
- 29 July 2020
- journal article
- review article
- Published by Springer Science and Business Media LLC in Signal Transduction and Targeted Therapy
- Vol. 5 (1), 1-17
- https://doi.org/10.1038/s41392-020-00242-3
Abstract
SOX2 is a well-characterized pluripotent factor that is essential for stem cell self-renewal, reprogramming, and homeostasis. The cellular levels of SOX2 are precisely regulated by a complicated network at the levels of transcription, post-transcription, and post-translation. In many types of human cancer, SOX2 is dysregulated due to gene amplification and protein overexpression. SOX2 overexpression is associated with poor survival of cancer patients. Mechanistically, SOX2 promotes proliferation, survival, invasion/metastasis, cancer stemness, and drug resistance. SOX2 is, therefore, an attractive anticancer target. However, little progress has been made in the efforts to discover SOX2 inhibitors, largely due to undruggable nature of SOX2 as a transcription factor. In this review, we first briefly introduced SOX2 as a transcription factor, its domain structure, normal physiological functions, and its involvement in human cancers. We next discussed its role in embryonic development and stem cell-renewal. We then mainly focused on three aspects of SOX2: (a) the regulatory mechanisms of SOX2, including how SOX2 level is regulated, and how SOX2 cross-talks with multiple signaling pathways to control growth and survival; (b) the role of SOX2 in tumorigenesis and drug resistance; and (c) current drug discovery efforts on targeting SOX2, and the future perspectives to discover specific SOX2 inhibitors for effective cancer therapy.Keywords
Funding Information
- National Key Laboratory of Science and Technology on Communications (2016YFA0501800)
- National Natural Science Foundation of China (81974429)
This publication has 264 references indexed in Scilit:
- Sox2 suppresses the invasiveness of breast cancer cells via a mechanism that is dependent on Twist1 and the status of Sox2 transcription activityBMC Cancer, 2013
- The Sox2 high mobility group transcription factor inhibits mature osteoblast function in transgenic miceBone, 2011
- The Hippo Signaling Pathway in Development and CancerDevelopmental Cell, 2010
- Autocrine TGF-β Signaling Maintains Tumorigenicity of Glioma-Initiating Cells through Sry-Related HMG-Box FactorsCell Stem Cell, 2009
- Tgfβ Signal Inhibition Cooperates in the Induction of iPSCs and Replaces Sox2 and cMycCurrent Biology, 2009
- Acquisition of Granule Neuron Precursor Identity Is a Critical Determinant of Progenitor Cell Competence to Form Shh-Induced MedulloblastomaCancer Cell, 2008
- Integration of External Signaling Pathways with the Core Transcriptional Network in Embryonic Stem CellsCell, 2008
- The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem CellsCell, 2008
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006
- Core Transcriptional Regulatory Circuitry in Human Embryonic Stem CellsCell, 2005