Cell Death and Disease (Apr 2021)

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

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

DOI
https://doi.org/10.1038/s41419-021-03630-x
Journal volume & issue
Vol. 12, no. 4
pp. 1 – 13

Abstract

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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.