HomeoboxC6 promotes metastasis by orchestrating the DKK1/Wnt/\u03b2-catenin axis in right-sided colon cancer

Lina Qi,Kailai Wang,Wangxiong Hu,Kailun Xu,Ying Yuan,Yingkuan Shao,Shu Zheng,Jiani Chen,Biting Zhou,Zhihao Fang

doi:10.1038/s41419-021-03630-x

Abstract

Patients with right-sided colon cancer (RCC) generally have a poorer prognosis than those with left-sided colon cancer (LCC). We previously found that homeobox C6 (HOXC6) was the most significantly upregulated gene in RCC compared to LCC. However, it remains unclear whether HOXC6 plays a role in tumor proliferation and metastasis. Our study aimed to explore the potential oncogenic role and the detailed molecular mechanism of HOXC6 in RCC. In this study, HOXC6 was validated to be overexpressed in RCC and associated with poor prognosis. Furthermore, overexpression of HOXC6 promoted the migration and invasion of colon cancer cells through inducing EMT by activating the Wnt/β-catenin signaling pathway and inhibition of DKK1 secretion. Lastly, we preliminary explored the translational effect of HOXC6 and found that silencing of HOXC6 made HCT116 and HT29 cells more sensitive to irinotecan.

Highlights

Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, and its incidence rate and mortality rate rank third among all malignant tumors worldwide[1]
We confirmed that homeobox C6 (HOXC6) was overexpressed in right-sided colon cancer (RCC) and associated with a worse outcome
HOXC6 was overexpressed in RCC and associated with poor prognosis

Summary

Introduction

Colorectal cancer (CRC) is one of the most common digestive tract malignant tumors, and its incidence rate and mortality rate rank third among all malignant tumors worldwide[1]. An increasing number of studies have revealed that left- and right-sided colon cancer (LCC and RCC) differ greatly in embryology, epidemiology, molecular characteristics, and clinical manifestations[2,3]. LCC and RCC patients that may better explain the worse survival of RCC remains poorly understood. We identified HOXC6 as the most significantly upregulated gene in RCC compared to LCC in both TCGA and GSE14333 datasets, indicating that HOXC6 may be an oncogene in RCC7. The concrete role of HOXC6 in RCC remains unknown, and whether HOXC6 may serve as a target in RCC to improve patient survival should be urgently clarified

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