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Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2

Year: 2005
Type: preprint
Abstract: The PTEN and TSC2 tumor suppressors inhibit mammalian target of rapamycin (mTOR) signaling and are defective in distinct hamartoma syndromes. Using mouse genetics, we find that Pten and Tsc2 act synergistically to suppress the severity of a subset of tumors specific to loss of each of these genes. Interestingly, we find that the slow-growing tumors specific to Tsc2+/- mice exhibit defects in signaling downstream of Akt. However, Pten haploinsufficiency restores Akt signaling in these tumors and dramatically enhances their severity. This study demonstrates that attenuation of the PI3K-Akt pathway in tumors lacking TSC2 contributes to their benign nature.
DOI: 10.1101/gad.1314605
Authors: Brendan D. Manning, M. Nicole Logsdon, Alex I. Lipovsky, Derek Abbott, David J. Kwiatkowski, Lewis C. Cantley
Language: English
Open Access status: diamond
Funders: American Cancer Society, Tuberous Sclerosis Alliance, Leukemia and Lymphoma Society, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke
Awards: G1419180683, G1697268722, G2541828554, G3002641176, The Role of PTEN and the PI3K Pathway in Prostate Cancer, Tuberous Sclerosis: Mutations and Murine Models, G9000060484
OpenAlex ID: W2086524655
Cites: 39
Cited by: 236
Related to: 10