[Can defective TGF-Beta signaling be an Achilles heel in human cancer?].
Survival signals in cancer cells activate mTOR-the mammalian target of rapamycin. mTOR suppresses TGF-beta signals that arrest cell cycle progression in late G1-thus activated mTOR prevents cell cycle arrest at a checkpoint mediated by TGF-beta. Rapamycin treatment resurrects TGF-beta signals causing G1 arrest. Defects in TGF-beta signaling are common in human cancer, and ironically, cancer cells with defective TGF-beta signaling that do not arrest in G1, instead undergo apoptosis when treated with rapamycin. Thus, defective TGF-beta signaling may represent an Achilles heel for rational therapeutic targeting of cancer cells using rapamycin-based strategies.
Foster
David A
DA
Department of Biological Sciences, Hunter College of the City University of New York, New York, NY, USA. foster@genectr.hunter.cuny.edu
Gadir
Noga
N
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D016193:G1 Phase; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000502:physiology*
D000903:Antibiotics, Antineoplastic; D047908:Intracellular Signaling Peptides and Proteins; D016212:Transforming Growth Factor beta; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus