p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion

Steven A. Hayes, Xiaoke Huang, Suman Kambhampati, Leonidas C. Platanias, Raymond Bergan

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Transforming growth factor beta (TGFβ) regulates cell adhesion, proliferation, and differentiation in a variety of cells. Smad proteins are receptor-activated transcription factors that translocate to the nucleus in response to TGFβ. We demonstrate here that TGFβ increases cell adhesion in metastatic PC3-M prostate cancer cells. TGFβ treatment of PC3-M cells leads to nuclear translocation of R-Smad proteins. We show that Smad proteins are necessary, but not sufficient, for TGFβ-mediated cell adhesion. After showing that TGFβ upregulated p38 MAP kinase activity in PC3-M cells, we show that inhibition of p38 MAP kinase partially blocked TGFβ-mediated increase in cell adhesion, as well as nuclear translocation of Smad3. Finally, we show that Smad3 is phosphorylated by p38 MAP kinase in vitro. These findings implicate crosstalk between the MAP kinase and Smad signaling pathways in TGFβ's regulation of cell adhesion in human prostate cells. This represents a mechanism by which the pleiotropic effects of TGFβ may be channeled to modulate cell adhesion.

Original languageEnglish (US)
Pages (from-to)4841-4850
Number of pages10
JournalOncogene
Volume22
Issue number31
DOIs
StatePublished - Jul 31 2003
Externally publishedYes

Fingerprint

p38 Mitogen-Activated Protein Kinases
Cell Adhesion
Transforming Growth Factor beta
Prostate
Smad Proteins
Receptor-Regulated Smad Proteins
MAP Kinase Signaling System
Cell Differentiation
Prostatic Neoplasms
Transcription Factors
Cell Proliferation

Keywords

  • Cell adhesion
  • p38 MAP kinase
  • Prostate cancer
  • Smad
  • Transforming growth factor beta

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion. / Hayes, Steven A.; Huang, Xiaoke; Kambhampati, Suman; Platanias, Leonidas C.; Bergan, Raymond.

In: Oncogene, Vol. 22, No. 31, 31.07.2003, p. 4841-4850.

Research output: Contribution to journalArticle

Hayes, SA, Huang, X, Kambhampati, S, Platanias, LC & Bergan, R 2003, 'p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion', Oncogene, vol. 22, no. 31, pp. 4841-4850. https://doi.org/10.1038/sj.onc.1206730
Hayes, Steven A. ; Huang, Xiaoke ; Kambhampati, Suman ; Platanias, Leonidas C. ; Bergan, Raymond. / p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion. In: Oncogene. 2003 ; Vol. 22, No. 31. pp. 4841-4850.
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