Enhanced PAPSS2/VCAN sulfation axis is essential for Snail-mediated breast cancer cell migration and metastasis.

ABSTRACT: The zinc finger protein Snail is a master regulator of epithelial-mesenchymal transition (EMT) and a strong inducer of tumor metastasis, yet the signal cascades triggered by Snail have not been completely revealed. Here, we report the discovery of the sulfation program that can be induced by Snail in breast cancer cells, and which plays an essential role in cell migration and metastasis. Specifically, Snail induces the expression of PAPSS2, a gene that encodes a rate-limiting enzyme in sulfation pathway, and VCAN, a gene that encodes the chondroitin sulfate proteoglycan Versican in multiple breast cancer cells. Depletion of PAPSS2 in MCF7 and MDA-MB-231 cells results in reduced cell migration, while overexpression of PAPSS2 promotes cell migration. Moreover, MDA-MB-231-shPAPSS2 cells displ

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC6370781 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature