Objective: Cancer stem cell (CSC) genes are emerging as cancer therapeutic targets. MUC1 is a cell surface-associated glycoprotein that is aberrantly over‐expressed in >60% of human cancers including breast cancer. Recent findings have also indicated significant upregulation of MUC1 in cancer cells. Differential glycosylation of MUC1 in cancer cells as compared to normal cells makes it a lucrative target to precisely identify and attack cancer cells. Many MUC1 targeting antibodies have been developed by various groups to target MUC1-overexpressing cells.

Materials and Methods: We analyzed several publicly available datasets to recognize the factors controlling MUC1 expression in CSCs and also analyze the possible regulation of MUC1 expression in CSCs.

Results: In this meta-analysis, we explore the positive correlation between CSC signature genes and MUC1 and further extrapolate the findings to speculate about the differential methylation pattern of the MUC1 core promoter region. Recent findings showed that SOX2 binding sites might undergo passive demethylation and SOX2 binding motifs can attract demethylases. We also predicted a SOX2 binding region on the MUC1 core promoter which further strengthened our analysis to explore new insights on MUC1 and SOX2 interplay in CSCs.

Conclusions: The need of the hour is to unveil the detailed mechanistic crosstalk between MUC1 and SOX2 which might give us a new direction to target the root cause of cancer relapse by disarming the CSCs.