| Literature DB >> 29955124 |
Yihong Zhang1,2, Xiuqun Zou1,2, Wenli Qian1,2, Xiaoling Weng3, Lin Zhang4, Liang Zhang4, Shuang Wang5, Xuan Cao6, Li Ma6, Gang Wei7, Yingjie Wu8, Zhaoyuan Hou9,10.
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 display a significantly lower rate of lung metastasis and lower number of micrometastatic nodules in nude mice, and conversely, MDA-MB-231-PAPSS2 cells increase lung metastasis. Similarly, depletion of VCAN dampens the cell migration activity induced by Snail or PAPSS2 in MCF 10A cells. Moreover, PAPSS inhibitor sodium chlorate effectively decreases cell migration induced by Snail and PAPSS2. More importantly, the expression of Snail, PAPSS2, and VCAN is positively correlated in breast cancer tissues. Together, these findings are important for understanding the genetic programs that control tumor metastasis and may identify previously undetected therapeutic targets to treat metastatic disease.Entities:
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Year: 2018 PMID： 29955124 PMCID： PMC6370781 DOI： 10.1038/s41418-018-0147-y
Source DB: PubMed Journal: Cell Death Differ ISSN： 1350-9047 Impact factor: 15.828