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

38 Citations (Scopus)

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

Unfolded Protein Response
Epithelial-Mesenchymal Transition
Interleukin-6
Carcinogenesis
Autocrine Communication
CCAAT-Enhancer-Binding Protein-beta
Breast Neoplasms
Cysteine Proteinase Inhibitors
Serine Proteinase Inhibitors
NF-kappa B
Neoplasms
Breast
Epithelial Cells
Cytokines
Inflammation
Phenotype

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Sheshadri, N., Catanzaro, J. M., Bott, A. J., Sun, Y., Ullman, E., Chen, E. I., ... 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

SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling. / Sheshadri, Namratha; Catanzaro, Joseph M.; Bott, Alex J.; Sun, Yu; Ullman, Erica; Chen, Emily I.; Pan, Ji An; Wu, Song; Crawford, Howard C.; Zhang, Jianhua; Zong, Wei Xing.

In: Cancer Research, Vol. 74, No. 21, 01.11.2014, p. 6318-6329.

Research output: Contribution to journalArticle

Sheshadri, N, Catanzaro, JM, Bott, AJ, Sun, Y, Ullman, E, Chen, EI, Pan, JA, Wu, S, Crawford, HC, Zhang, J & Zong, WX 2014, 'SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling', Cancer Research, vol. 74, no. 21, pp. 6318-6329. https://doi.org/10.1158/0008-5472.CAN-14-0798
Sheshadri, Namratha ; Catanzaro, Joseph M. ; Bott, Alex J. ; Sun, Yu ; Ullman, Erica ; Chen, Emily I. ; Pan, Ji An ; Wu, Song ; Crawford, Howard C. ; Zhang, Jianhua ; Zong, Wei Xing. / SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling. In: Cancer Research. 2014 ; Vol. 74, No. 21. pp. 6318-6329.
@article{124900308de5435482cf793b63292dba,
title = "SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling",
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.",
author = "Namratha Sheshadri and Catanzaro, {Joseph M.} and Bott, {Alex J.} and Yu Sun and Erica Ullman and Chen, {Emily I.} and Pan, {Ji An} and Song Wu and Crawford, {Howard C.} and Jianhua Zhang and Zong, {Wei Xing}",
year = "2014",
month = "11",
day = "1",
doi = "10.1158/0008-5472.CAN-14-0798",
language = "English (US)",
volume = "74",
pages = "6318--6329",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "21",

}

TY - JOUR

T1 - SCCA1/SERPINB3 promotes oncogenesis and epithelial-mesenchymal transition via the unfolded protein response and IL6 signaling

AU - Sheshadri, Namratha

AU - Catanzaro, Joseph M.

AU - Bott, Alex J.

AU - Sun, Yu

AU - Ullman, Erica

AU - Chen, Emily I.

AU - Pan, Ji An

AU - Wu, Song

AU - Crawford, Howard C.

AU - Zhang, Jianhua

AU - Zong, Wei Xing

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84909592613&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84909592613&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-14-0798

DO - 10.1158/0008-5472.CAN-14-0798

M3 - Article

C2 - 25213322

AN - SCOPUS:84909592613

VL - 74

SP - 6318

EP - 6329

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 21

ER -