Cellular signaling in normal and cancerous stem cells.
Self-renewing divisions of normal and cancerous stem cells are responsible for the initiation and maintenance of normal and certain cancerous tissues, respectively. Recent findings suggest that tumor surveillance mechanisms can reduce regenerative capacity and frequency of normal stem cells, thereby contributing to tissue aging. Signaling pathways promoting self-renewal of stem cells can also drive proliferation in cancer. The BMI-1 proto-oncogene is required for the maintenance of tissue-specific stem cells and is involved in carcinogenesis within the same tissues. BMI-1 promotes self-renewal of stem cells largely by interfering with two central cellular tumor suppressor pathways, p16(Ink4a)/retinoblastoma protein (Rb) and ARF/p53, whose disruption is a hallmark of cancer. Nucleolin, an Rb-associated protein, is abundant in proliferating cancerous cells and likely contributes to the maintenance of human CD34-positive stem/progenitor cells of hematopoiesis. Elucidation of the involvement of proto-oncogenes and tumor suppressors in the maintenance of stem cells might have therapeutic implications.
Grinstein
Edgar
E
Institute of Transplantation Diagnostics and Cellular Therapeutics, Heinrich Heine University Medical Center, 40225 Düsseldorf, Germany. edgar.grinstein@web.de
Wernet
Peter
P
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D016922:Cellular Senescence; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*; D000097796:Nucleolin
D020727:ADP-Ribosylation Factors; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D000097796:Nucleolin; C000715470:MAS1 protein, human