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Angiomotin-like 2 interacts with and negatively regulates AKT
1Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA, USA.
Oncogene
|April 4, 2017
Summary
Angiomotin-like 2 (AMOTL2) inhibits both YAP and AKT, crucial for liver size control. Its downregulation in liver cancer suggests a dual tumor suppressive role in preventing cancer.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Angiomotin-like 2 (AMOTL2) is known to inhibit the Hippo pathway effector YAP.
- The broader cellular functions of AMOTL2, beyond YAP inhibition, remain largely unexplored.
Purpose of the Study:
- To investigate the novel cellular functions of AMOTL2.
- To elucidate the role of AMOTL2 in liver physiology and hepatocellular carcinoma.
Main Methods:
- Co-immunoprecipitation assays to identify AMOTL2 interacting proteins.
- Analysis of liver-specific AMOTL2-deficient mouse models.
- Examination of AMOTL2 expression in human liver cancer tissues.
Main Results:
- AMOTL2 was identified as a negative regulator of AKT signaling.
- AMOTL2 binds to AKT, inhibiting its membrane localization and activation.
- Liver-specific AMOTL2 depletion led to liver enlargement and activation of both YAP and AKT pathways.
- Reduced AMOTL2 expression correlated with increased YAP and AKT activity in human liver cancers.
Conclusions:
- AMOTL2 possesses a dual tumor suppressive function by inhibiting both YAP and AKT.
- AMOTL2 plays a critical role in regulating liver size and preventing liver cancer development.
- Targeting AMOTL2 may offer a novel therapeutic strategy for liver cancer.