Cten promotes Epithelial–Mesenchymal Transition (EMT) in colorectal cancer through stabilisation of Src
| Autor: | Mohammad Ilyas, Abdulaziz Alfahed, Abdulaziz Asiri, Maham Akhlaq, Michael S. Toss, Hannah Thorpe, Teresa P Raposo, Abutaleb Asiri |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition Regulator Motility Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor Tensins medicine Humans Epithelial–mesenchymal transition Cell Proliferation Gene knockdown Oncogene Chemistry Microfilament Proteins General Medicine Gene Expression Regulation Neoplastic Genes src 030104 developmental biology Cell culture Gene Knockdown Techniques 030220 oncology & carcinogenesis Cancer research Signal transduction Colorectal Neoplasms Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Pathology International. 69:381-391 |
| ISSN: | 1440-1827 1320-5463 |
| DOI: | 10.1111/pin.12811 |
| Popis: | Cten is an oncogene promoting EMT in many signaling pathways, namely through Snail. We investigated whether Cten function could be mediated through Src. Cten levels were modulated by forced expression in HCT116 and gene knockdown in SW620 CRC (colorectal cancer) cell lines. In all cell lines, Cten was a positive regulator of Src expression. The functional importance of Src was tested by simultaneous Cten overexpression and Src knockdown. This resulted in abrogation of Cten motility-inducing activity and reduction of colony formation ability together with failure to induce Cten targets. In SW620ΔCten reduced Src expression increased following restoration of Cten, also leading to increased cell motility and colony formation, which were lost if Src was concomitantly knocked down. By qRT-PCR we showed modulation of Cten had no effect on Src mRNA. However, a CHX pulse chase assay demonstrated stabilization of Src protein by Cten. Finally, expression of Cten and Src was tested in a series of 84 primary CRCs and there was a significant correlation between them (P = 0.001). We conclude that Src is a novel and functionally important target of the Cten signaling pathway and that Cten protein causes post-transcriptional stabilization of Src in promoting EMT and possibly metastasis in CRC. |
| Databáze: | OpenAIRE |
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