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ポスター発表

第4日　5月18日（金）　　ポスター会場

4P-02　　PDF

Proteomic analysis reveals important role of O-GlcNAcylation in anoikis resistance and anchorage-independent growth of breast cancers

(¹CRI・ ²CGI・ ³OLARN)
^oNgernsuk, Pukkavadee¹・ Chaiyawat, Parunya³・ Chokchaichamnankit, Daranee¹・ Lirdprapamongkol, Kriengsak¹・ Srisomsap, Chantragan¹・ Svasti, Jisnuson^1,2・ Champattanachai, Voraratt^1,2

O-GlcNAcylation is a dynamic posttranslational modification of nuclear, cytoplasmic and mitochondrial proteins. Emerging evidence reveals that aberrant O-GlcNAcylation is associated with malignant phenotypes of breast cancer. However, the important roles of this modification in cancer development and progression remain unexplored. In this study, we aim to investigate the roles of O-GlcNAcylation in malignant transformations using breast cancer cell lines (MCF-7 and MDA-MB-231) as study models. We found that the levels of O-GlcNAcylation and O-GlcNAc transferase (OGT) were increased in cancerous cells when compared to those of normal breast cells (HMEC). OGT knockdown of MCF-7 caused a dramatic decrease in OGT and O-GlcNAcylation levels, resulting in the suppression of anchorage-independent growth and spheroid formation. Using 2-DE gel-based proteomics and LC-MS/MS analysis, several proteins from spheroid culturing were identified and compared. Among them, one of heat shock protein family was found to be highest-increased in OGT knockdown. Immunoblot analysis revealed that this protein level was up-regulated while its O-GlcNAc modification was down-regulated in OGT knockdown. Collectively, these results demonstrate that O-GlcNAcylation is required for malignant transformation. Blocking this glycosylation by OGT knockdown altered the expression and its O-GlcNAc modification of this heat shock protein, thus ultimately affecting malignant progression of breast cancer