Abstract 2384: CD151-integrin complexes suppress ovarian tumor growth by repressing slug-mediated emt and canonical wnt signaling

Abstract

Abstract The majority of human ovarian cancer is diagnosed in the late, metastatic stages and is highly resistant to current chemotherapies. The molecular and cellular mechanisms underlying the malignancy of ovarian cancer remain poorly understood. We report a surprising functional link between CD151-α31 integrin complexes and the malignancy of serous ovarian cancer. Analyses of clinical specimens indicate that CD151 expression is significantly reduced or diminished in approximately 90% of metastatic lesions, while it remains detectable in >40% of primary ovarian tumors. These observations suggest a putative tumor-suppressing role of CD151 in ovarian cancer. Indeed, our analyses with multiple ovarian cancer cell lines show that knocking down CD151 or α3β1 integrin markedly enhances tumor cell proliferation, growth and ascites production in nude mice. These changes are accompanied by impaired cell-cell contacts and aberrant expression of E-cadherin, Mucin 5AC and fibronectin, largely reminiscent of an epithelial to mesenchymal transition (EMT)-like change. Importantly, Slug, a master regulator of EMT, is markedly elevated upon CD151 removal. Knocking down Slug partially restores CD151-α3β1 integrin complex-dependent suppression of cell proliferation. Moreover, disruption of these adhesion protein complexes is accompanied by a concomitant activation of canonical Wnt signaling, including elevated levels of β-catenin and Axin-2 as well as resistance to the inhibition in β-catenin-dependent transcription complexes. Taken together, our study demonstrates that CD151-α3β1 integrin complexes suppress ovarian cancer malignancy by repressing Slug-mediated EMT and canonical Wnt signaling. Citation Format: Xiuwei H. Yang. CD151-integrin complexes suppress ovarian tumor growth by repressing slug-mediated emt and canonical wnt signaling. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2384. doi:10.1158/1538-7445.AM2015-2384