HNF6 promotes tumor growth in colorectal cancer and enhances liver metastasis in mouse model

J Cell Physiol. 2019 Apr;234(4):3675-3684. doi: 10.1002/jcp.27140. Epub 2018 Sep 7.

Abstract

Hepatocyte nuclear factor 6 (HNF6), as a transcription factor, has been reported to be involved in cell proliferation, carcinogenesis, and tumor metastasis. Here, we demonstrated the role of HNF6 in tumor growth and liver metastasis in colorectal cancer (CRC). Through bioinformatics and clinical samples analysis, we found HNF6 messenger RNA was upregulated both in CRC primary sites and liver metastases, and its high expression indicated poor survival in CRC patients. In vitro studies confirmed that HNF6 promoted cell proliferation and colony formation. What is more, in mouse models, the xenografts grew significantly faster and liver metastasis rate was nearly 45% higher in mice injected with HNF6-overexpressing cells. Further mechanism exploration showed that HNF6 expression affected cell adhesion and conferred resistance to anoikis in CRC cells. Taken together, HNF6 expression was upregulated in CRC and closely correlated with poor survival. HNF6 promoted CRC cell proliferation and tumor growth, and may contribute to liver metastasis via conferring cell resistance to anoikis.

Keywords: HNF6; anoikis; colorectal cancer; liver metastasis; tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anoikis
  • Cell Adhesion
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 6 / genetics
  • Hepatocyte Nuclear Factor 6 / metabolism*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Liver Neoplasms / secondary
  • Mice, Inbred BALB C
  • Mice, Nude
  • Signal Transduction
  • Tumor Burden
  • Up-Regulation

Substances

  • Hepatocyte Nuclear Factor 6
  • ONECUT1 protein, human