The commonality of plasticity underlying multipotent tumor cells and embryonic stem cells.
Aggressive cancer cells and pluripotent stem cells converge in their capacity for self-renewal, proliferation and plasticity. Recent studies have capitalized on these similarities by demonstrating that tumors arise from specific cancer stem cell populations that, in a manner reminiscent of normal stem cells, are able to both self-renew and give rise to a heterogeneous tumor population. This stem cell like function of aggressive cancer cells is likely attributable to the ectopic expression of embryonic factors such as Nodal and Cancer Testis Specific Antigens (CTAs), which maintain a functional plasticity by promoting pluripotency and immortality. During development, the expression of these embryonic factors is tightly regulated by a dynamic array of mediators, including the spatial and temporal expression of inhibitors such as Lefty, and the epigenetic modulation of the genome. In aggressive cancer cells, particularly melanoma, this balance of regulatory mediators is disrupted, leading to the aberrant expression of pluripotency-associated genes. By exposing aggressive cancer cells to embryonic microenvironments, this balance of regulatory mediators is restored, thereby reprogramming tumor cells to a more benign phenotype. These stem cell-derived mediators, as well as the genes they regulate, provide therapeutic targets designed to specifically differentiate and eradicate aggressive cancers.
Postovit
Lynne-Marie
LM
Program in Cancer Biology and Epigenomics, Children's Memorial Research Center, Northwestern University, Feinberg School of Medicine, Chicago, IL 60614, USA.
Costa
Fabricio F
FF
Bischof
Jared M
JM
Seftor
Elisabeth A
EA
Wen
Bo
B
Seftor
Richard E B
RE
Feinberg
Andrew P
AP
Soares
Marcelo Bento
MB
Hendrix
Mary J C
MJ
D019070:Cell Lineage; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D055458:Left-Right Determination Factors; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D055457:Nodal Protein; D039904:Pluripotent Stem Cells / Q000378:metabolism / Q000473:pathology*; D051785:Smad Proteins / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C526161:LEFTY1 protein, human; D055458:Left-Right Determination Factors; C526007:NODAL protein, human; D055457:Nodal Protein; D051785:Smad Proteins; D016212:Transforming Growth Factor beta