# 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

## TL;DR

This study explores how human mesenchymal stem cells' secretome can suppress colon cancer growth by targeting a specific signaling pathway involving IRSp53.

## Contribution

The study introduces hAMSCs secretome as a novel therapeutic approach for colon cancer by inhibiting the EGFR/c-Src/IRSp53 signaling cascade.

## Key findings

- IRSp53 is upregulated in colon cancer patient specimens.
- hAMSCs secretome suppresses tumor growth by inhibiting the EGFR/c-Src/IRSp53/p-AKT/p-Stat3/cyclin D1 pathway.
- 3D cell culture confirmed reduced proliferation in hAMSCs-treated HT-29 cells.

## 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.