MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression

Sheema Khan, M. Sikander, M. C. Ebeling, A. Ganju, S. Kumari, Murali Yallapu, Bilal Hafeez, T. Ise, S. Nagata, Nadeem Zafar, S. W. Behrman, Jim Wan, H. M. Ghimire, P. Sahay, P. Pradhan, Subhash Chauhan, Meena Jaggi

Research output: Contribution to journalArticle

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Abstract

Although MUC13, a transmembrane mucin, is aberrantly expressed in pancreatic ductal adenocarcinoma (PDAC) and generally correlates with increased expression of HER2, the underlying mechanism remains poorly understood. Herein, we found that MUC13 co-localizes and interacts with HER2 in PDAC cells (reciprocal co-immunoprecipitation, immunofluorescence, proximity ligation, co-capping assays) and tissues (immunohistofluorescence). The results from this study demonstrate that MUC13 functionally interacts and activates HER2 at p1248 in PDAC cells, leading to stimulation of HER2 signaling cascade, including ERK1/2, FAK, AKT and PAK1 as well as regulation of the growth, cytoskeleton remodeling and motility, invasion of PDAC cells-all collectively contributing to PDAC progression. Interestingly, all of these phenotypic effects of MUC13-HER2 co-localization could be effectively compromised by depleting MUC13 and mediated by the first and second EGF-like domains of MUC13. Further, MUC13-HER2 co-localization also holds true in PDAC tissues with a strong functional correlation with events contributing to increased degree of disorder and cancer aggressiveness. In brief, findings presented here provide compelling evidence of a functional ramification of MUC13-HER2: this interaction could be potentially exploited for targeted therapeutics in a subset of patients harboring an aggressive form of PDAC.

Original languageEnglish (US)
Pages (from-to)491-500
Number of pages10
JournalOncogene
Volume36
Issue number4
DOIs
StatePublished - Jan 26 2017

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Receptor Protein-Tyrosine Kinases
Adenocarcinoma
Mucins
Cytoskeleton
Immunoprecipitation
Epidermal Growth Factor
Fluorescent Antibody Technique
Ligation
Growth
Neoplasms

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression. / Khan, Sheema; Sikander, M.; Ebeling, M. C.; Ganju, A.; Kumari, S.; Yallapu, Murali; Hafeez, Bilal; Ise, T.; Nagata, S.; Zafar, Nadeem; Behrman, S. W.; Wan, Jim; Ghimire, H. M.; Sahay, P.; Pradhan, P.; Chauhan, Subhash; Jaggi, Meena.

In: Oncogene, Vol. 36, No. 4, 26.01.2017, p. 491-500.

Research output: Contribution to journalArticle

Khan, S, Sikander, M, Ebeling, MC, Ganju, A, Kumari, S, Yallapu, M, Hafeez, B, Ise, T, Nagata, S, Zafar, N, Behrman, SW, Wan, J, Ghimire, HM, Sahay, P, Pradhan, P, Chauhan, S & Jaggi, M 2017, 'MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression', Oncogene, vol. 36, no. 4, pp. 491-500. https://doi.org/10.1038/onc.2016.218
Khan, Sheema ; Sikander, M. ; Ebeling, M. C. ; Ganju, A. ; Kumari, S. ; Yallapu, Murali ; Hafeez, Bilal ; Ise, T. ; Nagata, S. ; Zafar, Nadeem ; Behrman, S. W. ; Wan, Jim ; Ghimire, H. M. ; Sahay, P. ; Pradhan, P. ; Chauhan, Subhash ; Jaggi, Meena. / MUC13 interaction with receptor tyrosine kinase HER2 drives pancreatic ductal adenocarcinoma progression. In: Oncogene. 2017 ; Vol. 36, No. 4. pp. 491-500.
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AU - Yallapu, Murali

AU - Hafeez, Bilal

AU - Ise, T.

AU - Nagata, S.

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AU - Behrman, S. W.

AU - Wan, Jim

AU - Ghimire, H. M.

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AU - Chauhan, Subhash

AU - Jaggi, Meena

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