American Association for Cancer Research
00085472can140798-sup-128685_2_supp_2590661_n9l6bx.pdf (2.1 MB)

Supplemental Materials and Methods, Figure Legend, Figures S1-6 from SCCA1/SERPINB3 Promotes Oncogenesis and Epithelial–Mesenchymal Transition via the Unfolded Protein Response and IL6 Signaling

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journal contribution
posted on 2023-03-30, 22:47 authored by 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

Supplemental Materials and Methods, Figure Legend, Figures S1-6. Figure S1. SCCA1-expressing MCF10A cells become independent of the hormonal factors. Figure S2. Expression of SCCA1 leads to IL-6 production. Figure S3. The induction of UPR by SCCA1 is dependent on its protease inhibition function. Figure S4. Silencing of ATF6a and PERK leads to decreased IL-6 production and cell proliferation in MDA-MB-231 cells. Figure S5. Silencing of SCCA results in decreased UPR, IL-6 production, and cell growth. Figure S6. Elevated SCCA1 expression leads to UPR and IL-6 production in various cell lines.



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-κB and IL6 autocrine signaling that promotes a protumorigenic inflammation. Cancer Res; 74(21); 6318–29. ©2014 AACR.