Common stemness regulators of embryonic and cancer stem cells

Abstract

Pluripotency of embryonic stem cells (ESCs) and induced pluripotent stem cells is regulated by a well characterized gene transcription circuitry. The circuitry is assembled by ESC specific transcription factors, signal transducing molecules and epigenetic regulators. Growing understanding of stem-like cells, albeit of more complex phenotypes, present in tumors (cancer stem cells), provides a common conceptual and research framework for basic and applied stem cell biology. In this review, we highlight current results on biomarkers, gene signatures, signaling pathways and epigenetic regulators that are common in embryonic and cancer stem cells. We discuss their role in determining the cell phenotype and finally, their potential use to design next generation biological and pharmaceutical approaches for regenerative medicine and cancer therapies.

Keywords: Cancer stem cells; Embryonic stem cells; Pluripotency; Self-renewal; Tumorigenicity.

Figure 1

Core signaling pathways in embryonic stem cells and cancer stem cells. A: Mouse ESCs require concerted LIF/BMP signaling to sustain self-renewal and pluripotency, whereas hESC pluripotency depends on the activity of the TGF-β and the FGF pathway. Wnt signaling is important for pluripotency in both species; B: Wnt, Hedgehog, Notch and FGF signaling pathways are associated with CSC self-renewal, while BMP signaling is implicated in CSC differentiation. The TGF-β/Activin/Nodal pathway has a controversial role in CSCs depending on cancer type. ESCs: Embryonic stem cells; CSCs: Cancer stem cells; hESC: Human ESCs; APC: Adenomatous polyposis coli; Dsh: Dishevelled; FGF: Fibroblast growth factor; GSK3: Glycogen synthase kinase 3; JAK: Janus-family tyrosine kinase; LRP: Lipoprotein receptor-related protein; PKC: Protein kinase C; SUFU: Suppressor of fused homolog; TCF/LEF: Tcell factor/Lymphocyte enhancer binding factor.