Abstract 2464: Angiomotin plays a tumor suppressor role by sequestering oncogenic YAP/TAZ proteins and decreasing amphiregulin secretion in lung cancer

Abstract

Abstract Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying the majority of lung cancer-related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic YAP/TAZ proteins, suggesting its potential role in tumor suppression. However, the functional role of AMOT in lung cancer remains unknown. We observed that the expression of AMOT was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreasing cytoplasmic sequestration and increasing nuclear translocation of oncogenic co-activators YAP/TAZ, resulting in an increased expression of the growth factor amphiregulin. The tumor promotion by AMOT knockdown was reversed when YAP/TAZ were absent or anti-amphiregulin antibodies were present. Further, AMOT knockdown increased the spread of Lewis lung carcinoma in vivo. Our findings suggest that AMOT is a crucial suppressor of lung cancer metastasis. These observations highlight the critical role of AMOT as a tumor suppressor, and the potential of AMOT as a prognostic biomarker and potential therapy target for lung cancer. Note: This abstract was not presented at the meeting. Citation Format: Po-Lin Kuo, Jen-Yu Hung, Ya-Ling Hsu. Angiomotin plays a tumor suppressor role by sequestering oncogenic YAP/TAZ proteins and decreasing amphiregulin secretion in lung cancer. [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 2464. doi:10.1158/1538-7445.AM2014-2464