SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling

Namratha Sheshadri, Joseph M. Catanzaro, Alex J. Bott, Yu Sun, Erica Ullman, Emily I. Chen, Ji An Pan, Song Wu, Howard C. Crawford, Jianhua Zhang, Wei Xing Zong

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

The serine/cysteine protease inhibitor SCCA1 (SERPINB3) 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), IL6 expression, and inflammatory phenotypes. Mechanistically, SCCA1 induced a prolonged nonlethal increase in the UPR that was sufficient to activate NF-κB and expression of the protumorigenic cytokine IL6. Overall, our findings established that SCCA1 contributes to tumorigenesis by promoting EMT and a UPR-dependent induction of NF-kB and IL6 autocrine signaling that promotes a protumorigenic inflammation.

Original languageEnglish (US)
Pages (from-to)6318-6329
Number of pages12
JournalCancer Research
Volume74
Issue number21
DOIs
StatePublished - Nov 1 2014

    Fingerprint

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sheshadri, N., Catanzaro, J. M., Bott, A. J., Sun, Y., Ullman, E., Chen, E. I., Pan, J. A., Wu, S., Crawford, H. C., Zhang, J., & Zong, W. X. (2014). SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling. Cancer Research, 74(21), 6318-6329. https://doi.org/10.1158/0008-5472.CAN-14-0798