Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway

C. S. Craft, D. Romero, C. P H Vary, Raymond Bergan

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Endoglin is a transforming growth factor β (TGFβ) superfamily auxiliary receptor. We had previously shown that it suppressed prostate cancer (PCa) cell motility, and that its expression was lost during PCa progression. The mechanism by which endoglin inhibits PCa cell motility is unknown. Here we demonstrate that endoglin abrogates TGFβ-mediated cell motility, but does not alter cell surface binding of TGFβ. By measuring Smad-specific phosphorylation and Smad-responsive promoter activity, endoglin was shown to constitutively activate Smad1, with little-to-no effect upon Smad3. Knockdown of Smad1 increased motility and abrogated endoglin's effects. As type I activin receptor-like kinases (ALKs) are necessary for Smad activation, we went on to show that knockdown of ALK2, but not TGFβRI (ALK5), abrogated endoglin-mediated decreases in cell motility and constitutively active ALK2 was sufficient to restore a low-motility phenotype in endoglin deficient cells. These findings provide the first evidence that endoglin decreases PCa cell motility through activation of the ALK2-Smad1 pathway.

Original languageEnglish (US)
Pages (from-to)7240-7250
Number of pages11
JournalOncogene
Volume26
Issue number51
DOIs
StatePublished - Nov 8 2007
Externally publishedYes

Fingerprint

Prostatic Neoplasms
Cell Movement
Transforming Growth Factors
Type I Activin Receptors
Endoglin
Phosphorylation
Phenotype

Keywords

  • ALK2
  • Endoglin
  • Motility
  • Prostate cancer
  • Smad1
  • Transforming growth factor β

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. / Craft, C. S.; Romero, D.; Vary, C. P H; Bergan, Raymond.

In: Oncogene, Vol. 26, No. 51, 08.11.2007, p. 7240-7250.

Research output: Contribution to journalArticle

Craft, C. S. ; Romero, D. ; Vary, C. P H ; Bergan, Raymond. / Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. In: Oncogene. 2007 ; Vol. 26, No. 51. pp. 7240-7250.
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