HOXA5-Mediated Stabilization of IκBα Inhibits the NF-κB Pathway and Suppresses Malignant Transformation of Breast Epithelial Cells.

ABSTRACT: HOXA5 is a transcription factor and tumor suppressor that promotes differentiation of breast epithelial cells and is frequently lost during malignant transformation. HOXA5 loss alone, however, does not confer tumorigenicity. To determine which molecular alterations combined with loss of HOXA5 expression can transform cells, we examined isogenic derivatives of a nonmalignant breast epithelial cell line containing knock-in or knockout mutations in key breast cancer genes. Knockdown (KD) of HOXA5 in cells harboring double knock-in (DKI) of mutated PIK3CA (E545K) and HER2 (V777L) induced epithelial-mesenchymal transition and migration and promoted invasive tumor outgrowth within mouse mammary ducts. The NF-κB pathway was significantly upregulated in DKI cells following HOXA5 KD. HOXA5 KD upreg

SUBMITTER: Pai P 

PROVIDER: S-EPMC9588663 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature