- Title
- Dissecting the signaling pathways that mediate cancer in PTEN and LKB1 double-knockout mice
- Creator
- Chen, Jiezhong; Zhang, Xu Dong; Proud, Christopher
- Relation
- NHMRC.APP1002857
- Relation
- Science Signaling Vol. 8, Issue 392
- Publisher Link
- http://dx.doi.org/10.1126/scisignal.aac8321
- Publisher
- American Association for the Advancement of Science (AAAS)
- Resource Type
- journal article
- Date
- 2015
- Description
- 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.
- Subject
- <i>PTEN</i>; <i>LKB1</i>; carcinogenesis; signaling pathways; cancer
- Identifier
- http://hdl.handle.net/1959.13/1314917
- Identifier
- uon:22856
- Identifier
- ISSN:1945-0877
- Language
- eng
- Reviewed
- Hits: 2714
- Visitors: 3135
- Downloads: 0
| Thumbnail | File | Description | Size | Format |
|---|