Abstract A25: WWOX phosphorylation at Ser14 enhances melanoma docking and growth in the lung and liver in mice

Abstract

Abstract Understanding of the fundamental cell behavior would help develop strategies for cancer stem cell eradication. Metastatic cancer cells tend to have epigenetically inactivated WWOX gene and are highly aggressive. Time-lapse microscopy revealed that they sense the surrounding WWOX-expressing normal or cancer cells, run away from them, and divide rapidly in order to survive. With time of growth and increased space pressure, these cancer cells grow as spheres with the expression of pluripotent stem cell markers such as Oct4, SSEA-4, TRA-1-60, and others. WWOX is re-expressed in the cancer stem cell spheres with S14 phosphorylation (pS14), suggesting that pS14WWOX is a potential cancer stem cell marker. Notably, organs, expressing pS14WWOX, are susceptible for melanoma cell docking and homing in vivo. Suppression of WWOX phosphorylation at Ser14 by micromolar levels of full-length Zfra1-31 or truncated Zfra4-10 prevents melanoma growth in the lung and liver in mice. Zfra stimulates non-T and non-B memory Hyal-2+ CD3- CD19- lymphocytes in the mouse spleens by binding to membrane hyaluronidase Hyal-2 and probably suppressing the TGF-beta/Hyal-2/WWOX/Smad4 signaling. In vitro education of Hyal-2+ CD3- CD19- cells suppresses melanoma growth in vivo. Citation Format: Wan-Pei Su, Wan-Jen Wang, Nan-Shan Chang. WWOX phosphorylation at Ser14 enhances melanoma docking and growth in the lung and liver in mice. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A25.