HOXB7 induces STAT3-mediated transformation and lung metastasis in immortalized mammary gland NMuMG cells

Genes Cells. 2023 Apr;28(4):277-287. doi: 10.1111/gtc.13009. Epub 2023 Jan 27.

Abstract

The homeobox family genes are often dysregulated in various cancer types. Particularly HOXB7 amplification and overexpression correlate with poor prognosis in various cancer such as gastric, pancreatic, and lung cancers. Moreover, HOXB7 is known to contribute to cancer progression by promoting epithelial to mesenchymal transition, anticancer drug resistance, and angiogenesis. In this study, we show that HOXB7 is coamplified with ERBB2 in a subset of breast cancer patients and HOXB7 expression correlates with poor prognosis in HER2-positive breast cancer patients. This clinical observation is supported by the following results-HOXB7 overexpression in an immortalized murine mammary gland epithelial cell line NMuMG induces cellular transformation in vitro, tumorigenesis, and lung metastasis through the activation of JAK-STAT signaling.

Keywords: ERBB2; HOXB7; NMuMG; breast cancer; metastasis; oncogene.

MeSH terms

  • Animals
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genes, Homeobox
  • Homeodomain Proteins / metabolism
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / pathology
  • Mammary Glands, Human* / metabolism
  • Mice
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism

Substances

  • Homeodomain Proteins
  • HOXB7 protein, human
  • STAT3 protein, human
  • STAT3 Transcription Factor