Inside the stemness engine: Mechanistic links between deregulated transcription factors and stemness in cancer

Cell identity is largely determined by its transcriptional profile. In tumour, deregulation of transcription factor expression and/or activity enables cancer cell to acquire a stem-like state characterised by capacity to self-renew, differentiate and form tumours in vivo. These stem-like cancer cells are highly metastatic and therapy resistant, thus warranting a more complete understanding of the molecular mechanisms downstream of the transcription factors that mediate the establishment of stemness state. Here, we review recent research findings that provide a mechanistic link between the commonly deregulated transcription factors and stemness in cancer. In particular, we describe the role of master transcription factors (SOX, OCT4, NANOG, KLF, BRACHYURY, SALL, HOX, FOX and RUNX), signalling-regulated transcription factors (SMAD, 13-catenin, YAP, TAZ, AP-1, NOTCH, STAT, GLI, ETS and NF-Kappa B) and unclassified transcription factors (c-MYC, HIF, EMT transcription factors and P53) across diverse tumour types, thereby yielding a comprehensive overview identifying shared downstream targets, highlighting unique mechanisms and discussing complexities.

Automated summary

Cell identity is determined by the transcriptional profile, and in cancer, deregulation of transcription factors allows cancer cells to acquire a stem-like state. These stem-like cancer cells are highly metastatic and therapy resistant. This article reviews recent research findings and describes the role of common transcription factors in maintaining the stemness state.