HOXA5-Mediated Stabilization of IkBa Inhibits the NF-kB Pathway and Suppresses Malignant Transformation of Breast Epithelial Cells

Priya Pai, Guannan Wang, Wei Wen Teo, Diana Raez-Rodriguez, Kathleen L. Gabrielson, Balazs Gyo rffy, Bradley M. Downs, Akanksha Aggarwal, Saraswati Sukumar

Research output: Contribution to journalArticlepeer-review


HOXA5 is a transcription factor and tumor suppressor that but not RNA, expression was reduced in HOXA5-KD cells. HOXA5 promotes differentiation of breast epithelial cells and is frequently bound and stabilized IkBa, forming a nuclear HOXA5-IkBa lost during malignant transformation. HOXA5 loss alone, however, complex. Chromatin immunoprecipitation sequencing database does not confer tumorigenicity. To determine which molecular queries revealed that HOXA5 and IkBa are co-enriched at 528 genoalterations combined with loss of HOXA5 expression can transform mic loci. In patients with breast cancer, high coexpression of cells, we examined isogenic derivatives of a nonmalignant breast HOXA5 and IkBa conferred a significantly better overall and epithelial cell line containing knock-in or knockout mutations in progression-free survival. Collectively, these data suggest that key breast cancer genes. Knockdown (KD) of HOXA5 in cells HOXA5 suppresses malignancy in breast epithelial cells by blunting harboring double knock-in (DKI) of mutated PIK3CA (E545K) NF-kB action via stabilization of its inhibitor IkBa. and HER2 (V777L) induced epithelial–mesenchymal transition and migration and promoted invasive tumor outgrowth within mouse Significance: Loss of HOXA5 reduces IkBa stability and mammary ducts. The NF-kB pathway was significantly upregulated increases NF-kB signaling to exacerbate breast cancer aggresin DKI cells following HOXA5 KD. HOXA5 KD upregulated siveness, providing new insights into the tumor suppressor multiple NF-kB target genes, including IL6. IkBa protein, functions of HOXA5.

Original languageEnglish (US)
Pages (from-to)3802-3814
Number of pages13
JournalCancer Research
Issue number20
StatePublished - Oct 15 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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