1. [Can defective TGF-Beta signaling be an Achilles heel in human cancer?].
- Author
-
Foster DA and Gadir N
- Subjects
- Antibiotics, Antineoplastic pharmacology, Cell Line, Tumor, G1 Phase, Humans, TOR Serine-Threonine Kinases, Transforming Growth Factor beta antagonists & inhibitors, Apoptosis, Intracellular Signaling Peptides and Proteins metabolism, Protein Serine-Threonine Kinases metabolism, Signal Transduction drug effects, Sirolimus pharmacology, Transforming Growth Factor beta physiology
- Abstract
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.
- Published
- 2008