TOR complex 2 is needed for cell cycle progression and anchorage-independent growth of MCF7 and PC3 tumor cells.
BACKGROUND
AKT signaling promotes cell growth, proliferation and survival and is hyperactivated in many cancers. TOR complex 2 (TORC2) activates AKT by phosphorylating it on the 'hydrophobic motif' site. Hydrophobic motif site phosphorylation is needed only for a subset of AKT functions. Whether proliferation of tumor cells depends on TORC2 activity has not been thoroughly explored.


METHODS
We used RNAi-mediated knockdown of rictor to inhibit TORC2 activity in MCF7 and PC3 tumor cells to analyze the importance of TORC2 on proliferation of tumor cells.


RESULTS
TORC2 inhibition reduced proliferation and anchorage-independent growth of both cell lines. Rictor depleted cells accumulated G1 phase, and showed prominent downregulation of Cyclin D1.


CONCLUSIONS
This study provides further evidence that inhibition of TORC2 activity might be a useful strategy to inhibit proliferation of tumor cells and subsequent tumor growth.
Hietakangas
Ville
V
Temasek Life Sciences Laboratory, 1 Research Link, The National University of Singapore, 117604, Singapore. ville@tll.org.sg
Cohen
Stephen M
SM
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D016193:G1 Phase / Q000502:physiology; D006801:Humans; D008297:Male; D051058:Oncogene Protein v-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D034622:RNA Interference; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
C493245:CRTC2 protein, human; D002352:Carrier Proteins; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D014157:Transcription Factors; D051058:Oncogene Protein v-akt