Tumor initiation via loss of cell contact inhibition versus Ras mutation: do all roads lead to EMT?
Many tumors have been found to contain a subset of cells referred to as cancer stem cells. As opposed to the remainder of the tumor, these cells are undifferentiated-they do not express markers of differentiation and they can re-express stem cell specification genes. The cells can divide asymmetrically to yield differentiated cells as well as cells comprising the original heterogeneous population of the tumor while maintaining their number. Because cancer stem cells display some properties of stem cells, it has been presumed that the presence of such cells in tumors reflects a stem cell origin for cancer. However, recent studies suggest that cancer can originate with outgrowth of differentiated somatic cells, and that cells with properties of cancer stem cells can be generated as tumors progress. Appearance of such cells may be linked to reprogramming of differentiated somatic cells to a stem cell-like phenotype by overexpression of transcription factors involved in epithelial-mesenchymal transition (EMT). We discuss recent studies from our group and other laboratories linking cell outgrowth in tumors to inhibition of the RB1 pathway, loss of cell contact inhibition and generation of undifferentiated cancer stem-like cells from somatic cells. And, we compare this pathway to that arising with introduction of mutant Ras in cells.
Liu
Yongqing
Y
Molecular Targets Program, James Graham Brown Cancer Center and Department of Ophthalmology, University of Louisville Health Sciences Center, Louisville, KY, USA.
Dean
Douglas C
DC
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D002454:Cell Differentiation; D018450:Disease Progression; D004847:Epithelial Cells / Q000166:cytology*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000071799:Zinc Finger E-box-Binding Homeobox 1; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D018631:ras Proteins