Abstract
Endoglin, a transmembrane glycoprotein that acts as a transforming growth factor-beta (TGF-beta) coreceptor, is downregulated in PC3-M metastatic prostate cancer cells. When restored, endoglin expression in PC3-M cells inhibits cell migration in vitro and attenuates the tumorigenicity of PC3-M cells in SCID mice, though the mechanism of endoglin regulation of migration in prostate cancer cells is not known. The current study indicates that endoglin is phosphorylated on cytosolic domain threonine residues by the TGF-beta type I receptors ALK2 and ALK5 in prostate cancer cells. Importantly, in the presence of constitutively active ALK2, endoglin did not inhibit cell migration, suggesting that endoglin phosphorylation regulated PC3-M cell migration. Therefore, our results suggest that endoglin phosphorylation is a mechanism with relevant functional consequences in prostate cancer cells. These data demonstrate for the first time that TGF-beta receptor-mediated phosphorylation of endoglin is a Smad-independent mechanism involved in the regulation of prostate cancer cell migration.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Activin Receptors, Type I / metabolism*
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Adenocarcinoma / metabolism
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Adenocarcinoma / pathology*
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Animals
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Antigens, CD / chemistry
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Antigens, CD / genetics
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Antigens, CD / physiology*
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Bone Morphogenetic Protein 7 / pharmacology
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Cell Line, Tumor / metabolism
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Cell Line, Tumor / transplantation
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Cell Movement / physiology
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Endoglin
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Female
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Humans
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Male
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Neoplasm Invasiveness
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Neoplasm Proteins / metabolism*
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Phosphorylation / drug effects
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Phosphothreonine / metabolism
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Prostatic Neoplasms / metabolism
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Prostatic Neoplasms / pathology*
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Protein Processing, Post-Translational / drug effects
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Protein Serine-Threonine Kinases / metabolism*
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Receptor, Transforming Growth Factor-beta Type I
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / physiology*
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Receptors, Transforming Growth Factor beta / metabolism*
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / physiology
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Sequence Deletion
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Transforming Growth Factor beta / physiology*
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Transforming Growth Factor beta1 / pharmacology
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Transplantation, Heterologous
Substances
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Antigens, CD
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BMP7 protein, human
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Bone Morphogenetic Protein 7
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ENG protein, human
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Endoglin
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Neoplasm Proteins
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Receptors, Cell Surface
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Receptors, Transforming Growth Factor beta
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Recombinant Fusion Proteins
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Transforming Growth Factor beta
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Transforming Growth Factor beta1
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Phosphothreonine
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Protein Serine-Threonine Kinases
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ACVR1 protein, human
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Activin Receptors, Type I
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Receptor, Transforming Growth Factor-beta Type I
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TGFBR1 protein, human
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Tgfbr1 protein, mouse