Fig. 7: Working model of OCT4A in somatic cancer cells.

In somatic cancer cells, authentic OCT4A proteins are heterogeneously expressed at very low levels in the cell nucleus. The trace amount of OCT4A proteins directly and preferentially bind to a distal enhancer region (green box, located at “Enhancer”) of FOS that has not been identified before, positively regulate the transcription of FOS and critically maintain its expression level, and thereby regulating numerous downstream genes (FOS target genes). The OCT4A-regulated genes in somatic cancer cells that are fundamentally distinct from those in PSCs play key roles in cell migration, propagation, tumorigenesis and chemoresistance, etc. There is an indication that at higher expression levels, OCT4A proteins may differentially bind to other octamer motifs on FOS (green boxes, located at “Promoter” and “Intron”), either inhibiting (“−”) or promoting (“ + ”) the transcription of FOS. The numbered yellow boxes stand for the four exons of FOS gene