Antibodies Against Specific MUC16 Glycosylation Sites Inhibit Ovarian Cancer Growth

Thapi Dharma Rao, Alberto Fernández-Tejada, Abram Axelrod, Nestor Rosales, Xiujun Yan, Sahityasri Thapi, Amy Wang, Kay J. Park, Brandon Nemieboka, Jingyi Xiang, Jason S. Lewis, Narciso Olvera, Douglas A. Levine, Samuel J. Danishefsky, David R. Spriggs

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Expression of the retained C-terminal extracellular portion of the ovarian cancer glycoprotein MUC16 induces transformation and tumor growth. However, the mechanisms of MUC16 oncogenesis related to glycosylation are not clearly defined. We establish that MUC16 oncogenic effects are mediated through MGAT5-dependent N-glycosylation of two specific asparagine sites within its 58 amino acid ectodomain. Oncogenic signaling from the C-terminal portion of MUC16 requires the presence of Galectin-3 and growth factor receptors colocalized on lipid rafts. These effects are blocked upon loss of either Galectin-3 expression or activity MGAT5. Using synthetic MUC16 glycopeptides, we developed novel N-glycosylation site directed monoclonal antibodies that block Galectin-3-mediated MUC16 interactions with cell surface signaling molecules. These antibodies inhibit invasion of ovarian cancer cells, directly blocking the in vivo growth of MUC16-bearing ovarian cancer xenografts, elucidating new therapeutic modalities.

Original languageEnglish
Pages (from-to)2085-2096
Number of pages12
JournalACS Chemical Biology
Issue number8
StatePublished - 18 Aug 2017
Externally publishedYes


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