# Functional Characterization of Suppressor of Cytokine Signalling 6 and Its Interaction with Erythropoietin Receptor in Colorectal Cancer Cells

## TL;DR

This study explores how SOCS6 and EPOR interact in colorectal cancer cells, revealing their complex roles in cancer growth and survival.

## Contribution

The study identifies a regulatory feedback loop between SOCS6 and EPOR in colorectal cancer, suggesting new therapeutic strategies.

## Key findings

- SOCS6 silencing increases cell viability and migration in colorectal cancer cells.
- EPOR knockdown alters SOCS6 expression, indicating a regulatory feedback loop.
- EPOR silencing affects cell viability differently over time in different cell lines.

## Abstract

Suppressor of Cytokine Signalling 6 (SOCS6) is a cytokine signalling suppressor that regulates receptor tyrosine kinase pathways to control cell growth and survival and has been implicated as a tumour suppressor in colorectal cancer. Erythropoietin Receptor (EPOR) plays a significant role in promoting tumour proliferation and angiogenesis in colorectal cancer (CRC). However, their interaction remains unexamined, and the roles of SOCS6 and EPOR in CRC are poorly understood. This study investigates the molecular mechanisms of SOCS6 in CRC pathogenesis and its association with EPOR expression after gene knockdown. The findings reveal that reducing SOCS6 increases cancer cell survival and migration, while changes in EPOR expression influence SOCS6 levels and cell survival differently depending on the cell type. This research highlights the complex relationship between SOCS6 and EPOR in colorectal cancer and suggests that targeting their interaction may offer new, personalized treatment strategies in colorectal cancer.

Background: Suppressor of Cytokine Signalling 6 (SOCS6) is a cytokine signalling suppressor that regulates receptor tyrosine kinase pathways by promoting degradation of signalling proteins, thereby controlling cell growth and survival. One of these tyrosine kinase receptors, Erythropoietin Receptor (EPOR), plays a critical role in CRC progression by enhancing tumour metabolism, angiogenesis, proliferation, and growth. This study investigates the molecular mechanisms governing SOCS6’s role in CRC pathogenesis using in vitro cell models and examines its interaction with EPOR expression following gene knockdown. Methods: Bioinformatics interaction between SOCS6 and EPOR were investigated using molecular visualization. HT-29 and COLO 320DM colorectal cancer cells were transfected with SOCS6 siRNA followed by measurement of SOCS6 and EPOR expression levels by qRT-PCR. The selected knockdown concentration was used in functional assays assessing cell viability, colony formation, migration, apoptosis, and invasion. Results: Bioinformatic results showed interaction between SOCS6 and EPOR through polar bonds. Furthermore, SOCS6 silencing increased cell viability and colony formation in both cell lines and significantly enhanced migration in COLO 320DM cells. Active caspase-3 levels were elevated markedly in HT-29 cells post SOCS6 knockdown, consistent with caspase-3’s reported oncogenic role in CRC. Moreover, EPOR knockdown selectively altered SOCS6 expression in HT-29 cells, indicating a regulatory feedback loop. EPOR silencing elevated cell viability at 24 h in both cell lines but caused a significant decrease in COLO 320DM cells at 72 h. Conclusions: These findings identify the SOCS6–EPOR axis as a potential target for personalized CRC therapy, supporting SOCS6’s tumour-suppressive and diagnostic roles.