Abstract
Colon cancer is the fifth leading cause of cancer-related deaths worldwide. Stem cells have unique characteristics and are considered as a novel therapeutic platform for cancer. Sugen Kinase 269 (SgK269) is considered as an oncogenic scaffolding pseudo kinase which governs the rearranging of the cytoskeleton, cellular motility, and invasion. The aim of this study is to evaluate the expression of SgK269 in colon cancer patients and explore the therapeutic effects of human amniotic mesenchymal stromal cells (hAMSCs) on invasion and proliferation of colon cancer cells (HT-29) through analyzing SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2 signaling pathway. In this regard, we collected 30 samples from colon cancer patients and evaluated SgK269 expression using quantitative real-time PCR (qRT-PCR). Next, we employed a co-culture system using Transwell 6-well plates and after 72 h, tumor growth promotion and invasion were analyzed in hAMSCs-treated HT-29 cells through SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac signaling pathway using qRT-PCR, western blot method, MTT assay, wound healing assay, and DAPI staining. Our results showed upregulation of SgK269 in colon cancer patients. Treatment of HT-29 colon cancer cells with hAMSCs secretome can inhibit SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac signaling pathway and the resulting suppression of cell invasion and proliferation. Our results suggest that SgK269 is an important target in colon cancer therapy and MSCs secretome may be an effective therapeutic approach to inhibit colon cancer cell invasion and proliferation through SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2/Rac signaling pathway.
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The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.
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Acknowledgements
We would like to thank Dr. S. Fakhrieh Asl, Dr. F. Mansour-Ghanaei, and all participants in Gastrointestinal and Liver Disease Research Center and Caspian Digestive Diseases Research Center, Rasht, Iran) for helping us collect patient samples.
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FS: designed the research and performed the experiments. FS, FOD and HD: analyzed data. FS: wrote the paper.
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The study protocols and experimental design parameters were reviewed and approved by University of Guilan (IR.GUILAN.REC.1401.017).
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Safari, F., Ansari Dogaheh, F. & Dadashi, H. Evaluation of SgK269 expression in colon cancer patients and the effects of hAMSCs secretome on tumor invasion through SgK269/c-Src/p-P130Cas/p-Paxillin/p-ERK1/2 signaling pathway in HT-29 colon cancer cells. 3 Biotech 13, 346 (2023). https://doi.org/10.1007/s13205-023-03763-0
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DOI: https://doi.org/10.1007/s13205-023-03763-0