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https://hdl.handle.net/2440/97750
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Type: | Journal article |
Title: | Dissecting the signaling pathways that mediate cancer in PTEN and LKB1 double-knockout mice |
Author: | Chen, J. Zhang, X.D. Proud, C. |
Citation: | Science Signaling, 2015; 8(392):pe1-1-pe1-3 |
Publisher: | American Association for the Advancement of Science |
Issue Date: | 2015 |
ISSN: | 1945-0877 1937-9145 |
Statement of Responsibility: | Jiezhong Chen, Xu Dong Zhang, Christopher Proud |
Abstract: | Double knockout of PTEN and LKB1-genes encoding phosphatase and tensin homolog and liver kinase B1, respectively-leads to the spontaneous development of cancer in mice. PTEN converts phosphatidylinositol (3,4,5)-trisphosphate (PIP3) to phosphatidylinositol (4,5)-bisphosphate (PIP2), whereas LKB1 activates the 5' adenosine monophosphate-activated protein kinase (AMPK). The kinase AKT and the kinase complex mTORC1 may play key roles in carcinogenesis and are components of signaling pathways that also contain PTEN and LKB1. We propose that via activation of AKT and mTORC1, the double knockout of PTEN and LKB1 contributes to distinct cell-specific aspects of tumor development and progression. Whereas mTORC1 promotes cancer initiation and progression through cell growth, survival, and proliferation, independent induction of the immune inhibitory molecule PD-L1 by activated AKT enables the tumors to evade immunosurveillance. |
Keywords: | Animals Mice, Knockout Mice Neoplasms Multiprotein Complexes Signal Transduction Cell Proliferation Cell Survival Tumor Escape Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase AMP-Activated Protein Kinases TOR Serine-Threonine Kinases Mechanistic Target of Rapamycin Complex 1 Protein Serine-Threonine Kinases |
Rights: | Copyright 2016 by the American Association for the Advancement of Science; all rights reserved. |
DOI: | 10.1126/scisignal.aac8321 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1002857 |
Published version: | http://dx.doi.org/10.1126/scisignal.aac8321 |
Appears in Collections: | Aurora harvest 3 Molecular and Biomedical Science publications |
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