MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells

Pallavi Chaturvedi, Ajay P. Singh, Subhankar Chakraborty, Subhash Chauhan, Sangeeta Bafna, Jane L. Meza, Pankaj K. Singh, Michael A. Hollingsworth, Parmender P. Mehta, Surinder K. Batra

Research output: Contribution to journalArticle

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Abstract

MUC4, a high-molecular weight transmembrane glycoprotein, is overexpressed in pancreatic cancer and is implicated in its pathogenesis. It is a heterodimeric protein containing a large extracellular, heavily glycosylated subunit, MUC4α, and a transmembrane growth factor-like subunit, MUC4β. In the present study, we have shown the interaction of human MUC4 with the receptor tyrosine kinase HER2 in pancreatic adenocarcinoma cells by reciprocal coimmunoprecipitation and cocapping studies. MUC4 colocalized with HER2 at the cell surface and in the cytoplasm. Silencing of MUC4 by transient or stable expression of MUC4-targeted short-interfering RNA led to the down-regulation of HER2 with a concomitant decrease in its phosphorylated form (pY1248-HER2). Further analyses revealed that the MUC4-knockdown-mediated decrease in HER2 expression occurred due to the drop in the stability of the receptor. In MUC4-knockdown pancreatic cancer cells, we also observed a reduced phosphorylation of the focal adhesion kinase and p42/44 mitogen-activated protein kinase, which are downstream effector proteins in HER2 signaling. Our findings add a new dimension to MUC4 function as a modulator of cell signaling and provide mechanistic evidence for its role in pancreatic cancer progression.

Original languageEnglish (US)
Pages (from-to)2065-2070
Number of pages6
JournalCancer Research
Volume68
Issue number7
DOIs
StatePublished - Apr 1 2008

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Oncogene Proteins
Mucins
Pancreatic Neoplasms
Focal Adhesion Protein-Tyrosine Kinases
Mitogen-Activated Protein Kinase 1
Receptor Protein-Tyrosine Kinases
Small Interfering RNA
Intercellular Signaling Peptides and Proteins
Glycoproteins
Cytoplasm
Proteins
Adenocarcinoma
Down-Regulation
Molecular Weight
Phosphorylation

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Chaturvedi, P., Singh, A. P., Chakraborty, S., Chauhan, S., Bafna, S., Meza, J. L., ... Batra, S. K. (2008). MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. Cancer Research, 68(7), 2065-2070. https://doi.org/10.1158/0008-5472.CAN-07-6041

MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. / Chaturvedi, Pallavi; Singh, Ajay P.; Chakraborty, Subhankar; Chauhan, Subhash; Bafna, Sangeeta; Meza, Jane L.; Singh, Pankaj K.; Hollingsworth, Michael A.; Mehta, Parmender P.; Batra, Surinder K.

In: Cancer Research, Vol. 68, No. 7, 01.04.2008, p. 2065-2070.

Research output: Contribution to journalArticle

Chaturvedi, P, Singh, AP, Chakraborty, S, Chauhan, S, Bafna, S, Meza, JL, Singh, PK, Hollingsworth, MA, Mehta, PP & Batra, SK 2008, 'MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells', Cancer Research, vol. 68, no. 7, pp. 2065-2070. https://doi.org/10.1158/0008-5472.CAN-07-6041
Chaturvedi, Pallavi ; Singh, Ajay P. ; Chakraborty, Subhankar ; Chauhan, Subhash ; Bafna, Sangeeta ; Meza, Jane L. ; Singh, Pankaj K. ; Hollingsworth, Michael A. ; Mehta, Parmender P. ; Batra, Surinder K. / MUC4 mucin interacts with and stabilizes the HER2 oncoprotein in human pancreatic cancer cells. In: Cancer Research. 2008 ; Vol. 68, No. 7. pp. 2065-2070.
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