A pivotal role for HOXB7 protein in endocrine resistant breast cancer

Kideok Jin, Saraswati Sukumar

Research output: Contribution to journalArticlepeer-review

Abstract

HOXB7 is a homeodomain containing transcription factor which plays a pivotal role in tamoxifen resistant breast cancer. Our work has shown that overexpression of HOXB7 renders cells tamoxifen resistant by mobilizing a number of receptor tyrosine kinase pathways. EGFR expression is upregulated by direct binding of HOXB7 to the EGFR promoter, while HOXB7 functions as a cofactor with ERa to cause overexpression of multiple ER-target genes, including HER2, in tamoxifen resistant breast cancer cells. Probing the pathway further, we found that miR-196a and MYC are upstream regulators of HOXB7 expression. Mechanistically, HOXB7 and ERa jointly upregulate HER2 which phosphorylates MYC. Thus stabilized, MYC in turn suppresses miR-196a. Loss of miR-196a results lifts the quelling influence of miR-196a on HOXB7 expression. Besides shedding light on the intricate interplay of events occurring in tamoxifen resistant breast cancer, the work identifies a number of new therapeutic targets capable of restoring sensitivity of breast cancer cells to tamoxifen.

Original languageEnglish (US)
Pages (from-to)917-919
Number of pages3
JournalOncoscience
Volume2
Issue number11
DOIs
StatePublished - 2015

Keywords

  • Breast cancer
  • ER
  • HOXB7
  • MYC
  • Tamoxifen-resistance

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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