MUC13 mucin augments pancreatic tumorigenesis

Subhash Chauhan, Mara C. Ebeling, Diane M. Maher, Michael D. Koch, Akira Watanabe, Hiroyuki Aburatani, Yuhlong Lio, Meena Jaggi

Research output: Contribution to journalArticle

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Abstract

The high death rate of pancreatic cancer is attributed to the lack of reliable methods for early detection and underlying molecular mechanisms of its aggressive pathogenesis. Although MUC13, a newly identified transmembrane mucin, is known to be aberrantly expressed in ovarian and gastro-intestinal cancers, its role in pancreatic cancer is unknown. Herein, we investigated the expression profile and functions of MUC13 in pancreatic cancer progression. The expression profile of MUC13 in pancreatic cancer was investigated using a recently generated monoclonal antibody (clone PPZ0020) and pancreatic tissue microarrays. The expression of MUC13 was significantly (P < 0.005) higher in cancer samples compared with normal/nonneoplastic pancreatic tissues. For functional analyses, full-length MUC13 was expressed in MUC13 null pancreatic cancer cell lines, MiaPaca and Panc1. MUC13 overexpression caused a significant (P < 0.05) increase in cell motility, invasion, proliferation, and anchorage-dependent or -independent clonogenicity while decreasing cell-cell and cell-substratum adhesion. Exogenous MUC13 expression significantly (P < 0.05) enhanced pancreatic tumor growth and reduced animal survival in a xenograft mouse model. These tumorigenic characteristics correlated with the upregulation/phosphorylation of HER2, p21-activated kinase 1 (PAK1), extracellular signal-regulated kinase (ERK), Akt, and metastasin (S100A4), and the suppression of p53. Conversely, suppression of MUC13 in HPAFII pancreatic cancer cells by short hairpin RNA resulted in suppression of tumorigenic characteristics, repression of HER2, PAK1, ERK, and S100A4, and upregulation of p53. MUC13 suppression also significantly (P < 0.05) reduced tumor growth and increased animal survival. These results imply a role of MUC13 in pancreatic cancer and suggest its potential use as a diagnostic and therapeutic target.

Original languageEnglish (US)
Pages (from-to)24-33
Number of pages10
JournalMolecular Cancer Therapeutics
Volume11
Issue number1
DOIs
StatePublished - Jan 1 2012

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Mucins
Pancreatic Neoplasms
Carcinogenesis
p21-Activated Kinases
Extracellular Signal-Regulated MAP Kinases
Up-Regulation
Intestinal Neoplasms
Neoplasms
Growth
Heterografts
Cell Adhesion
Small Interfering RNA
Cell Movement
Clone Cells
Monoclonal Antibodies
Phosphorylation
Cell Line
Mortality

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chauhan, S., Ebeling, M. C., Maher, D. M., Koch, M. D., Watanabe, A., Aburatani, H., ... Jaggi, M. (2012). MUC13 mucin augments pancreatic tumorigenesis. Molecular Cancer Therapeutics, 11(1), 24-33. https://doi.org/10.1158/1535-7163.MCT-11-0598

MUC13 mucin augments pancreatic tumorigenesis. / Chauhan, Subhash; Ebeling, Mara C.; Maher, Diane M.; Koch, Michael D.; Watanabe, Akira; Aburatani, Hiroyuki; Lio, Yuhlong; Jaggi, Meena.

In: Molecular Cancer Therapeutics, Vol. 11, No. 1, 01.01.2012, p. 24-33.

Research output: Contribution to journalArticle

Chauhan, S, Ebeling, MC, Maher, DM, Koch, MD, Watanabe, A, Aburatani, H, Lio, Y & Jaggi, M 2012, 'MUC13 mucin augments pancreatic tumorigenesis', Molecular Cancer Therapeutics, vol. 11, no. 1, pp. 24-33. https://doi.org/10.1158/1535-7163.MCT-11-0598
Chauhan S, Ebeling MC, Maher DM, Koch MD, Watanabe A, Aburatani H et al. MUC13 mucin augments pancreatic tumorigenesis. Molecular Cancer Therapeutics. 2012 Jan 1;11(1):24-33. https://doi.org/10.1158/1535-7163.MCT-11-0598
Chauhan, Subhash ; Ebeling, Mara C. ; Maher, Diane M. ; Koch, Michael D. ; Watanabe, Akira ; Aburatani, Hiroyuki ; Lio, Yuhlong ; Jaggi, Meena. / MUC13 mucin augments pancreatic tumorigenesis. In: Molecular Cancer Therapeutics. 2012 ; Vol. 11, No. 1. pp. 24-33.
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