SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling.
SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling.
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DOI：
10.1158/0008-5472.can-14-0798
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发表时间：
2014-11-01
期刊：
影响因子：
11.2
通讯作者：
Zong WX
中科院分区：
文献类型：
--
作者：
Sheshadri N;Catanzaro JM;Bott AJ;Sun Y;Ullman E;Chen EI;Pan JA;Wu S;Crawford HC;Zhang J;Zong WX
The serine/cysteine protease inhibitor SCCA1 (Serpin B3) is upregulated in many advanced cancers with poor prognosis, but there is limited information about whether it makes functional contributions to malignancy. Here we show that SCCA1 expression promoted oncogenic transformation and epithelial-mesenchymal transition (EMT) in mammary epithelial cells, and that SCCA1 silencing in breast cancer cells halted their proliferation. SCCA1 overexpression in neu+ mammary tumors increased the unfolded protein response (UPR), IL-6 expression, and inflammatory phenotypes. Mechanistically, SCCA1 induced a prolonged non-lethal increase in the UPR that was sufficient to activate NF-κB and expression of the pro-tumorigenic cytokine IL-6. Overall, our findings established that SCCA1 contributes to tumorigenesis by promoting EMT and a UPR-dependent induction of NF-κB and IL-6 autocrine signaling that promotes a pro-tumorigenic inflammation.
