Targeting oncogenic SOX2 in human cancer cells: therapeutic application

摘要

Sry-related high-mobility box 2 (SOX2) is a critical transcription factor that plays an important role in various phases of embryonic development and maintenance of undifferentiated embryonic stem cells (ESCs) (Feng and Wen, 2015). SOX2, as one of the Yamanaka factors, is involved in the conversion of mouse embryonic fibroblast cells (MEFs) into induced pluripotent stem cells (iPSCs) (Takahashi and Yamanaka, 2006). Recently, SOX2 amplification, usually couples with aberrantly increased expression, were found in various human cancers, including breast, lung, esophagus, colon, prostate, ovarian among the others (Novak et al., 2019). SOX2 overexpression promotes cancer progression by accelerating cell proliferation, colony formation, migration, invasion, and sphere formation. Furthermore, SOX2 is causally related to the development of the resistance of cancer cells to chemotherapy, radiotherapy and targeted therapy in different types of human cancers, likely due to its ability to maintain the stemness of cancer stem cells (CSCs), which are defined as a subpopulation within tumor cells being equipped with stem cell-like properties that survives the treatment and initiates tumor progression (Novak et al., 2019). Thus, SOX2 has been validated as an attractive anticancer target (Huser et al., 2018).