Platelet-derived growth factor receptor β-mediated phosphorylation of MUC1 enhances invasiveness in pancreatic adenocarcinoma cells

Pankaj Singh, Yunfei Wen, Benjamin J Swanson, Kandavel Shanmugam, Andrius Kazlauskas, Ronald Cerny, Sandra J. Gendler, Michael A Hollingsworth

Research output: Contribution to journalArticle

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Abstract

MUC1 is a heterodimeric transmembrane glycoprotein that is overexpressed and aberrantly glycosylated in ductal adenocarcinomas. Differential phosphorylation of the MUC1 cytoplasmic tail (MUC1CT) has been associated with signaling events that influence the proliferation and metastasis of cancer cells. We identified a novel tyrosine phosphorylation site (HGRYVPP) in the MUC1CT by mass spectrometric analysis of MUC1 from human pancreatic adenocarcinoma cell lines. Analyses in vitro and in vivo showed that platelet-derived growth factor receptor β (PDGFRβ) catalyzed phosphorylation of this site and of tyrosine in the RDTYHPM site. Stimulation of S2-013.MUC1F cells with PDGF-BB increased nuclear colocalization of MUC1CT and β-catenin. PDGF-BB stimulation had no significant effect on cell proliferation rate; however, it enhanced invasion in vitro through Matrigel and in vivo tumor growth and metastases. Invasive properties of the cells were significantly altered on expression of phosphorylation-abrogating or phosphorylation-mimicking mutations at these sites. We propose that interactions of MUC1 and PDGFRβ induce signal transduction events that influence the metastatic properties of pancreatic adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)5201-5210
Number of pages10
JournalCancer Research
Volume67
Issue number11
DOIs
StatePublished - Jun 1 2007

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Platelet-Derived Growth Factor Receptors
Adenocarcinoma
Phosphorylation
Tail
Tyrosine
Neoplasm Metastasis
Catenins
Signal Transduction
Neoplasms
Glycoproteins
Cell Proliferation
Cell Line
Mutation
Growth

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Platelet-derived growth factor receptor β-mediated phosphorylation of MUC1 enhances invasiveness in pancreatic adenocarcinoma cells. / Singh, Pankaj; Wen, Yunfei; Swanson, Benjamin J; Shanmugam, Kandavel; Kazlauskas, Andrius; Cerny, Ronald; Gendler, Sandra J.; Hollingsworth, Michael A.

In: Cancer Research, Vol. 67, No. 11, 01.06.2007, p. 5201-5210.

Research output: Contribution to journalArticle

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AU - Singh, Pankaj

AU - Wen, Yunfei

AU - Swanson, Benjamin J

AU - Shanmugam, Kandavel

AU - Kazlauskas, Andrius

AU - Cerny, Ronald

AU - Gendler, Sandra J.

AU - Hollingsworth, Michael A

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