Functional characterization of SOX2 as an anticancer target

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 posttranslation.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.