Overexpression of YY1 Regulates the Resistance of Cancer Stem Cells: Targeting YY1

Abstract

Most human cancers respond poorly to conventional therapeutics, and those that respond develop resistance to subsequent treatments. It has been reported that in many, but not all, studied cancers, there exists a mini population of cancer stem cells (CSCs) that is highly drug resistant and that its survival leads to recurrences and metastases. Hence, new targeted therapies directed at CSCs have been the subject of many investigations, and several agents are currently being investigated clinically. Several transcription factors are overexpressed in CSCs (e.g., SOX2, OCT4, NANOG, BMI1) that regulate stemness such as pluripotency and also regulate drug resistance. The transcription factor Yin Yang 1 (YY1) has been reported to be overexpressed in many cancers and is associated with cell proliferation, viability, EMT, metastasis, and chemo-immune resistance. Due to many common features of YY1 activities and cancer stem cell transcription factors, it was hypothesized that a crosstalk may exist between YY1 and CSCs transcription factors. Proteomic analysis was performed for the expression of YY1, SOX2, OCT4, and BM1 and delineated the presence of four groups of cancers with different molecular signatures consisting of different levels of expression of the above four transcription factors. These findings supported the hypothesis that YY1 is involved in the regulation of cancer stem cell transcription factors and their roles in resistance. Thus, targeting YY1 alone may be considered as a new therapeutic approach when used alone or in combination with various conventional or novel drugs to reverse cancer resistance in patients.