Cancers grow within tissues through molecular mechanisms still unclear. Invasiveness correlates with perturbed O-glycosylation, a covalent modification of cell-surface proteins. Here, we show that, in human and mouse liver cancers, initiation of O-glycosylation by the GALNT glycosyl-transferases increases and shifts from the Golgi to the endoplasmic reticulum (ER). In a mouse liver cancer model, expressing an ER-targeted GALNT1 (ER-G1) massively increased tumor expansion, with median survival reduced from 23 to 10 weeks. In vitro cell growth was unaffected, but ER-G1 strongly enabled matrix degradation and tissue invasion. Unlike its Golgi-localized counterpart, ER-G1 glycosylates the matrix metalloproteinase MMP14, a process required for tumor expansion. Together, our results indicate that GALNTs strongly promote liver tumor growth after relocating to the ER.

中文翻译：

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细胞器特异的O-糖基化驱动MMP14激活，肿瘤生长和转移。

癌症通过分子机制在组织内生长仍然不清楚。侵袭性与摄动的O-糖基化（细胞表面蛋白的共价修饰）相关。在这里，我们表明，在人类和小鼠肝癌中，GALNT糖基转移酶引发的O-糖基化增加并从高尔基体向内质网（ER）转移。在小鼠肝癌模型中，表达靶向ER的GALNT1（ER-G1）大大增加了肿瘤的扩展，中位生存期从23周减少到10周。体外细胞生长不受影响，但ER-G1强烈使基质降解和组织浸润。与位于高尔基体的对应物不同，ER-G1对基质金属蛋白酶MMP14进行糖基化，这是肿瘤扩张所需的过程。一起，