Focal adhesion molecule Kindlin-1 mediates activation of TGF-ß signaling by interacting with TGF-ßRI, SARA and Smad3 in colorectal cancer cells.
Oncotarget
; 7(46): 76224-76237, 2016 11 15.
Article
em En
| MEDLINE
| ID: mdl-27776350
ABSTRACT
Kindlin-1, an integrin-interacting protein, has been implicated in TGF-ß/Smad3 signaling. However, the molecular mechanism underlying Kindlin-1 regulation of TGF-ß/Smad3 signaling remains elusive. Here, we reported that Kindlin-1 is an important mediator of TGF-ß/Smad3 signaling by showing that Kindlin-1 physically interacts with TGF-ß receptor I (TßRI), Smad anchor for receptor activation (SARA) and Smad3. Kindlin-1 is required for the interaction of Smad3 with TßRI, Smad3 phosphorylation, nuclear translocation, and finally the activation of TGF-ß/Smad3 signaling pathway. Functionally, Kindlin-1 promoted colorectal cancer (CRC) cell proliferation in vitro and tumor growth in vivo, and was also required for CRC cell migration and invasion via an epithelial to mesenchymal transition. Kindlin-1 was found to be increased with the CRC progression from stages I to IV. Importantly, raised expression level of Kindlin-1 correlates with poor outcome in CRC patients. Taken together, we demonstrated that Kindlin-1 promotes CRC progression by recruiting SARA and Smad3 to TßRI and thereby activates TGF-ß/Smad3 signaling. Thus, Kindlin-1 is a novel regulator of TGF-ß/Smad3 signaling and may also be a potential target for CRC therapeutics.
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Base de dados:
MEDLINE
Assunto principal:
Serina Endopeptidases
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Neoplasias Colorretais
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Transdução de Sinais
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Fator de Crescimento Transformador beta
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Proteínas Serina-Treonina Quinases
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Receptores de Fatores de Crescimento Transformadores beta
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Peptídeos e Proteínas de Sinalização Intracelular
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Proteína Smad3
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Proteínas de Membrana
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Proteínas de Neoplasias
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article