Tuberous sclerosis complex: linking cancer to metabolism.
The TSC1/TSC2 tumor-suppressor complex regulates cell growth via controlling the mTOR (mammalian target of rapamycin) signaling pathway, which contributes to several disease processes, including cancer and diabetes. Abnormal activation of mTOR uncouples anabolic cell growth processes such as protein and lipid synthesis from external growth factor or nutrient cues. However, abnormal activation of mTOR upon loss of TSC1/TSC2 complex function is now known to lead to compensatory mechanisms that restrict the development of malignant tumors. The rare occurrence of complete loss of TSC1/TSC2 function in human tumors suggests that retaining growth suppressor activity might be beneficial during tumour evolution, perhaps by promoting survival when cells grow in a nutrient-limited environment.
Mieulet
Virginie
V
Department of Oncology, University of Alberta, Edmonton, Alberta, T6G 1Z2, Canada.
Lamb
Richard F
RF
D000818:Animals; D049109:Cell Proliferation; D025461:Feedback, Physiological; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D011506:Proteins; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D046912:Multiprotein Complexes; D011506:Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases