LAUSR

O-mannosylation of a-dystroglycan (α-DG) is an important modification in most tissues in mammals and plays diverse roles, from acting as viral receptors to neuronal development. The glycosylation produces a laminin-binding glycan (matriglycan) identified in nearly all epithelial cells in a differentiation-related manner. Reduction or loss of matriglycan has been implicated in cancer development and metastasis, and specifically associated with high-grade tumors and poor prognoses in breast cancers. Enhancing matriglycan expression has been proposed as potential therapeutics. In the current study, we demonstrate that ribitol, considered to be an end product of metabolism, increases levels of CDP-ribitol, the substrate for the ribitol-5-phosphate transferases FKRP and FKTN, and consequently significantly enhances the expression of matriglycan in the MCF7 breast cancer cells. This effect is FKRP and LARGE dependent and ribitol treatment does not alter the expression of glycosyltransferases known to be critical for the synthesis of matriglycan. Enhanced expression of matriglycan is related to cell cycle progression with highest levels in S and G2 phases. This is the first time that glycosylation of a-DG is shown to be up-regulated in cancer cells by a metabolite. Our data show another layer of modulation and illustrate the complexity of matriglycan expression in cancer cell proliferation and progression. Citation Format: qi L Lu, Pei J Lu, Jason D Tucker, Elizabeth K Branch, Fei Guo, Anthony R Blaeser. Ribitol enhances O-mannosylation of α-DG in breast cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr C024. doi:10.1158/1535-7163.TARG-19-C024