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PMID: 19595306 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

PI3K/PTEN signaling in angiogenesis and tumorigenesis.

Advances in cancer research ·Vol. 102 ·2009-00-00 ·Pages 19-65

Jiang BH, Liu LZ

Abstract

Phosphatidylinositol 3-kinase (PI3K) and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) signaling pathway play an important role in multiple cellular functions such as cell metabolism, proliferation, cell-cycle progression, and survival. PI3K is activated by growth factors and angiogenesis inducers such as vascular endothelial growth factor (VEGF) and angiopoietins. The amplification and mutations of PI3K and the loss of the tumor suppressor PTEN are common in various kinds of human solid tumors. The genetic alterations of upstream and downstream of PI3K signaling molecules such as receptor tyrosine kinases and AKT, respectively, are also frequently altered in human cancer. PI3K signaling regulates tumor growth and angiogenesis by activating AKT and other targets, and by inducing HIF-1 and VEGF expression. Angiogenesis is required for tumor growth and metastasis. In this review, we highlight the recent studies on the roles and mechanisms of PI3K and PTEN in regulating tumorigenesis and angiogenesis, and the roles of the downstream targets of PI3K for transmitting the signals. We also discuss the crosstalk of these signaling molecules and cellular events during tumor growth, metastasis, and tumor angiogenesis. Finally, we summarize the potential applications of PI3K, AKT, and mTOR inhibitors and their outcome in clinical trials for cancer treatment.

MeSH Terms
Animals Humans Neoplasms/blood supply,metabolism,pathology Neovascularization, Pathologic/enzymology PTEN Phosphohydrolase/metabolism Phosphatidylinositol 3-Kinases/metabolism Phosphoinositide-3 Kinase Inhibitors Signal Transduction/physiology
Chemicals
Phosphoinositide-3 Kinase Inhibitors PTEN Phosphohydrolase
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Jiang Bing-Hua
Mary Babb Randolph Cancer Center and Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, West Virginia 26506, USA.
Liu Ling-Zhi
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Article Info
Journal
Advances in cancer research
Abbr.
Adv Cancer Res
ISSN
2162-5557
DOI
10.1016/S0065-230X(09)02002-8
Published
2009-00-00
Pages
19-65
Language
English
Region
United States
NLM ID
0370416
PMCID
PMC2933405
Subset
IM
Grants
NCI NIH HHS · R01 CA109460-01A2 · United States
NCI NIH HHS · R01 CA109460-03 · United States
NHLBI NIH HHS · R01 HL091456-02 · United States
NIEHS NIH HHS · R21 ES017237-03 · United States
NHLBI NIH HHS · R01 HL091456-01 · United States
NIEHS NIH HHS · R21 ES017237 · United States
NIEHS NIH HHS · ES017237 · United States
NCI NIH HHS · R01 CA109460 · United States
NCI NIH HHS · R01 CA109460-05 · United States
NHLBI NIH HHS · R01 HL091456 · United States
NIEHS NIH HHS · R21 ES017237-01 · United States
NCI NIH HHS · R01 CA109460-04 · United States
NCI NIH HHS · R01 CA109460-02 · United States
NHLBI NIH HHS · HL091456 · United States
NIEHS NIH HHS · R21 ES017237-02 · United States
NCI NIH HHS · CA109460 · United States
External Links
PubMed source DOI: 10.1016/S0065-230X(09)02002-8 PMC Full Text
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