The Elevation of IRSp53 Expressing Level in Colon Cancer Specimens and the Secretome of hAMSCs’ Therapeutic Impacts on Tumor Growth Promotion via Inhibiting of EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 Signaling Cascade in HT‐29 Colon Cancerous Cell Line

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Abstract
Cancer is a predominant testimony of human departure in a global way. Current therapeutic strategies are not sufficient, and thereby exploring a new approach with high efficacy and influence is desired. The intention of this research is to distinguish a novel therapeutic burgeon in colon cancer plus employing the human mesenchymal stem cells (hAMSCs) secretome as a new tool in colon cancer therapy. For this purpose, 30 pieces from patients afflicted with colon cancer were provided. The expressing level of IRSp53 was evaluated using quantitative real‐time PCR (qRT‐PCR). Then, a coculture procedure utilizing six well plates transwell was applied. Since 72 h, tumor increment was surveyed in HT‐29 cells treated by hAMSCs through the EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 signaling cascade. Our results indicated IRSp53 upregulation in patients suffering colon cancer and reduction of EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 signaling pathway, which led to suppression of cell proliferation in the hAMSCs‐treated HT‐29 colon cancerous cells. We also found tumor growth suppression as well as IRSp53 expression in hAMSCs‐treated HT‐29 colon cancerous cell line using a 3D cell culturing technique. Our study’s findings indicate that colon cancer therapy could benefit from targeting IRSp53 and that MSCs could be a valuable therapeutic option for stopping the proliferation of colon cancer cells. This could be achieved through the EGFR/c‐Src/IRSp53/p‐AKT/p‐Stat3/cyclin D1 signaling pathway.

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