IRTKS Elevation in Patients with Colon Cancer and the Curative Influences of Hamsc Secretome on Polarity and Invasion of HT-29 Colon Cancer Cells

Purpose

Colon cancer is a major contributor (fifth one) to cancer-related deaths in the world. For the unique characteristics of stem cells, stem cells are considered to be a hopeful platform in cancer therapy. The current study aimed to examine the expression of insulin receptor tyrosine kinase substrate (IRTKS) in patients with colon cancer and seek therapy-related influences of human amniotic mesenchymal stromal cells (hAMSCs) on polarity and invasion of the human colon adenocarcinoma cell line HT-29 through measuring the core polarity proteins such as Snail, Lkb1, aPKC, Par3, Par6, Cdcd42, Scrib, Dlg, and Lgl expression.

Methods

Thirty colon cancer specimens were collected, and IRTKS expressions were evaluated by the utility of quantitative real-time PCR (qRT-PCR). Then, we engaged a co-culture method using six-well Transwell plates, and by passing 72 h, cell invasion and polarity were checked in the HT-29 cells treated in an hAMSC-associated manner utilizing qRT-PCR and western blot, as well as a wound-healing assay.

Results

Our findings indicated that up-regulation of IRTKS in patients with colon cancer and induction of Lkb1, aPKC, Par3, Par6, Scrib, and Dlg expression and reduction of Snail, Lgl, and Cdc42 expression in hAMSC-cured HT-29 colon cancer cells.

Conclusion

Our observations imply that IRTKS may be a valuable target in colon cancer treatment and hAMSC secretome enables the suppressing of colon cancer cells through cell invasion suppression and maintenance of cell polarity.

Lay Summary

The results of the current research displayed the up-regulation of IRTKS in colon cancer patients. It suggests a new biomarker in colon cancer diagnosis. We also found that the hAMSC secretome enables EMT inhibition and cell polarity maintenance through elevation of Lkb1/aPKC/Par3/Par6/Scrib/Dlg expression and reduction of IRTKS, Lgl, and Cdc42 expression in HT-29 colon cancer cells. Our findings indicate that the hAMSC secretome has curative influences on cancerous cells.

Graphical Abstract