Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis

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Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis
Title:
Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis
Journal Title:
Cancer Cell
Keywords:
Publication Date:
13 November 2017
Citation:
Organelle Specific O-Glycosylation Drives MMP14 Activation, Tumor Growth, and Metastasis Nguyen, Anh Tuan et al. Cancer Cell, Volume 32, Issue 5, 639 - 653.e6
Abstract:
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.
License type:
PublisherCopyrights
Funding Info:
This research is supported by core funding from the Institute of Molecular and Cell Biology.
Description:
The full paper is available for download at the publisher's URL: https://doi.org/10.1016/j.ccell.2017.10.001
ISSN:
1535-6108
1878-3686
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