Signal Transduction and Cancer: Regulation of Cellular Proliferation, Survival and Apoptosis
Cellular transformation, an early step in tumorigenesis, is almost exclusively caused by malfunction of signal transduction pathways. Immediate cellular environment, including metabolic, mitogenic and positional clues, activity of various modifier genes, as well as selective pressure for tumor growth, profoundly affects cellular signaling throughput and plays key roles in cancer initiation, progression and metastasis. Our laboratory is interested in studying cancer-related signal transduction and its effects on cellular growth, survival and apoptosis. Our primary interest is the PI3K signaling pathway, which has been implicated in the etiology of multiple human malignancies. For instance, PI3K (PIK3A) is a potent oncogene whose mutations are often found in colon, breast, brain and lung cancers, whereas PTEN, a gene whose protein product directly counteracts PI3K activity, is one of the most frequently mutated tumor suppressor genes in a variety of human cancers.
Our previous research in this area included characterization of the physiological function of PTEN, as well as development of several animal model systems that were highly informative in characterizing the role of 3’PI signaling in tumorigenesis and regulation of cell growth and size. More recently, we have become interested in the relevance of subcellular localization of pathway components as an additional regulatory input into 3’PI signaling and have described the importance of compartmentalization of certain pathway components for proper signal propagation Our current interests include examination of modes of PTEN regulation, prioritization of PKB/Akt substrates relevant to tumorigenesis and characterization of Rheb, a small GTPase and a downstream target of this pathway.Our work aims to provide a thorough understanding of molecular mechanisms of signal transduction and may lead to the development of effective therapeutic strategies for treatment of cancer.
Graduate Students:
- Christian Bassi
- Vanessa Di Palma
- Nasir Haider
- Tamara Maiuri
- Larissa Moniz
Selected References:
Link to Pubmed Publications-
Stambolic V. and Woodgett, JW Functional Distinctions of Protein Kinase B/Akt Isoforms Defined by Their Influence on Cell Migration. Trends in Cell Biology 2006, 16(9):461-6
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Buerger C, Devries B, Stambolic V. Localization of Rheb to the endomembrane is critical for its signaling function. Biochem Biophys Res Commun. 2006 J344(3):869-80
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Backman SA, Ghazarian D, So K, Sanchez O, Wagner KU, Hennighausen L, Suzuki A, Tsao MS, Chapman WB, Stambolic V, Mak TW. Early onset of neoplasia in the prostate and skin of mice with tissue-specific deletion of Pten. Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1725-30.
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Stambolic V, Suzuki A, de la Pompa JL, Brothers GM, Mirtsos C, Sasaki T, Ruland J, Penninger JM, Siderovski DP, Mak TW. Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN. Cell 1998, Vol. 95:29-39.
