ST6Gal-I–mediated sialylation of the epidermal growth factor receptor modulates cell mechanics and enhances invasion

• DOI: 10.1016/j.jbc.2022.101726
• Publication Date: 2022-02-12T07:14:37Z
• Authors: Tejeshwar C. Rao; Reena R. Beggs; Katherine E. Anke...; Jihye Hwang; Victor Pui-Yan Ma; Khalid Salaita; Susan L. Bellis; Alexa L. Mattheyses
• Keywords: Ovarian Neoplasms; Integrins; 0303 health sciences; Sialyltransferases; 3. Good health; ErbB Receptors; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; Female; beta-D-Galactoside alpha 2-6-Sialyltransferase; Research Article

Heterogeneity within the glycocalyx influences cell adhesion mechanics and signaling. However, role of specific glycosylation subtypes in influencing via alterations receptor function remains unexplored. It has been shown that addition sialic acid to terminal glycans impacts growth, development, cancer progression. In addition, sialyltransferase ST6Gal-I promotes epidermal growth factor (EGFR) activity, we have EGFR is an 'allosteric mechano-organizer' integrin tension. Here, investigated impact on mechanics. Using DNA-based tension gauge tether probes variable thresholds, found high activity increased forces spreading Cos-7 OVCAR3, OVCAR5, OV4 cells. Further, employing inhibitors function-blocking antibodies against β1, β3, β5 integrins targets EGFR, tumor necrosis receptor, Fas surface death validated observed phenotypes are EGFR-specific. We while tension, contractility, extracellular-signal-regulated kinase pathway-dependent, spreading, proliferation, invasion phosphoinositide 3-kinase-Akt serine/threonine dependent. total internal reflection fluorescence microscopy flow cytometry, also show leads sustained membrane retention, making it a key regulator Our findings suggest novel sialylation-dependent mechanism orchestrating cellular enhancing motility