HOXA13 promotes colon cancer progression through β-catenin-dependent WNT pathway

Exp Cell Res. 2020 Oct 15;395(2):112238. doi: 10.1016/j.yexcr.2020.112238. Epub 2020 Aug 18.

Abstract

Human class I homeobox A13 (HOXA13) was initially identified as a transcription factor and has an important role in embryonic development and malignant transformation. However, the clinical significance and the molecular mechanisms of HOXA13 in colon cancer development and progression are still unknown. In this study, we found that HOXA13 was highly expressed in colon cancer tissues, and its expression was associated with histological grade, T stage, N stage and tumour size. In vitro studies showed that HOXA13 promoted colon cancer cell proliferation, migration and invasion. Bioinformatics analysis revealed that HOXA13 expression was positively correlated with the WNT signalling pathway. In vitro studies showed that HOXA13 promoted the malignant phenotype of colon cancer cells by facilitating the nuclear translocation of β-Catenin. Moreover, XAV939, an inhibitor of β-Catenin, reversed the HOXA13-mediated effects on invasion and proliferation of colon cancer cells. In vivo studies further verified that HOXA13 promoted tumour formation through the Wnt/β-Catenin pathway. Collectively, these results suggest that HOXA13 is a potential oncogene that functions by promoting the nuclear translocation of β-Catenin, thereby maintaining the proliferation and metastasis of colon cancer.

Keywords: Cancer progression; Colon cancer; HOXA13; Wnt/β-Catenin signalling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cell Transformation, Neoplastic / genetics
  • Colon / metabolism
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / metabolism*

Substances

  • Homeodomain Proteins
  • beta Catenin
  • homeobox protein HOXA13