Cancer cells must degrade normal surrounding tissue in order to proliferate. We have found that this process is highly dependent on an increase in protein glycosylation induced by a signalling pathway nicknamed GALA. GALA is activated by the Src oncogene, which activates subcellular relocation of glycosylation enzymes. Hyper-glycosylated surface proteins endow cancer cells with the ability to degrade ECM. In particular, through the activation of proteases, but also through the activation of cell surface reductases, which reduces disulfide bonds in the ECM. GALA also appears to help cancer cells to out-compete normal epithelial cells. These processes can be inhibited by targeting cell surface glycoproteins. These results highlight the near-universal importance of glycosylation regulation in tumour biology and reveal new avenues for therapeutic intervention.
Published on January 17, 2022