HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis

Tetsu Hayashida, Fumiyuki Takahashi, Naokazu Chiba, Elena Brachtel, Motomi Takahashi, Nadia Godin-Heymann, Kenneth W. Gross, Maria D.M. Vivanco, Vasuki Wijendran, Toshihiro Shioda, Dennis Sgroi, Patricia K. Donahoe, Shyamala Maheswaran

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

The mechanisms underlying tumoral secretion of signaling molecules into the microenvironment, which modulates tumor cell fate, angiogenesis, invasion, and metastasis, are not well understood. Aberrant expression of transcription factors, which has been implicated in the tumorigenesis of several types of cancers, may provide a mechanism that induces the expression of growth and angiogenic factors in tumors, leading to their local increase in the tumor microenvironment, favoring tumor progression. In this report, we demonstrate that the transcription factor HOXB9 is overexpressed in breast carcinoma, where elevated expression correlates with high tumor grade. HOXB9 induces the expression of several angiogenic factors (VEGF, bFGF, IL-8, and ANGPTL-2), as well as ErbB (amphiregulin, epiregulin, and neuregulins) and TGF-ß, which activate their respective pathways, leading to increased cell motility and acquisition of mesenchymal phenotypes. In vivo, HOXB9 promotes the formation of large, well-vascularized tumors that metastasize to the lung. Thus, deregulated expression of HOXB9 contributes to breast cancer progression and lung metastasis by inducing several growth factors that alter tumor-specific cell fates and the tumor stromal microenvironment.

Original languageEnglish
Pages (from-to)1100-1105
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number3
DOIs
Publication statusPublished - 2010 Jan 19

Keywords

  • Angiogenesis
  • Breast cancer
  • Epithelial to mesenchymal transition
  • ErbB
  • TGF-β

ASJC Scopus subject areas

  • General

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  • Cite this

    Hayashida, T., Takahashi, F., Chiba, N., Brachtel, E., Takahashi, M., Godin-Heymann, N., Gross, K. W., Vivanco, M. D. M., Wijendran, V., Shioda, T., Sgroi, D., Donahoe, P. K., & Maheswaran, S. (2010). HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proceedings of the National Academy of Sciences of the United States of America, 107(3), 1100-1105. https://doi.org/10.1073/pnas.0912710107