Angiomotin (AMOT) is a member of the motin family that consists of three members, AMOT, AMOTL1, and AMOTL2, which function as either positive or negative regulators of cell growth depending on interacting proteins and cellular context. The role of AMOT in prostate cancer (PCa) has not been studied. AMOT is expressed as two isoforms, AMOTp80 and AMOTp130. The AMOTp130 isoform has an extended 409 aa N-terminal domain that is absent in AMOTp80. Both AMOTp80 and AMOTp130 are expressed in LNCaP and C4-2B4, but at a very low level in PC3-mm2 PCa cells. We found that expression of AMOTp130 and AMOTp80 have distinct functions in PCa cells. While AMOTp80 functions as a tumor promoter by enhancing PCa cell proliferation, AMOTp130 did not. We further show that AMOTp80 affects the Hippo tumor suppressor pathway by inhibiting LATS1 and YAP phosphorylation, resulting in nuclear translocation of YAP. Once in the nucleus, YAP increases transcription of the target protein BMP4. Moreover, inhibition of BMP receptor activity by LDN-193189 abrogates AMOTp80-mediated proliferation. These observations suggest that AMOTp80 induces the expression of BMP4, which functions in an autocrine manner to promote PCa cell proliferation. Together, our studies identify AMOTp80-MST-LATS1-YAP-BMP4 as a novel signal pathway that regulates PCa cell proliferation.
Citation Format: Angelica Ortiz, Hao Zeng, Sue-Hwa Lin. Angiomotin regulates the Hippo pathway to increase prostate cancer cell growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3307. doi:10.1158/1538-7445.AM2014-3307