TY - JOUR
T1 - HOXA5-Mediated Stabilization of IkBa Inhibits the NF-kB Pathway and Suppresses Malignant Transformation of Breast Epithelial Cells
AU - Pai, Priya
AU - Wang, Guannan
AU - Teo, Wei Wen
AU - Raez-Rodriguez, Diana
AU - Gabrielson, Kathleen L.
AU - Gyo rffy, Balazs
AU - Downs, Bradley M.
AU - Aggarwal, Akanksha
AU - Sukumar, Saraswati
N1 - Publisher Copyright:
2022 American Association for Cancer Research.
PY - 2022/10/15
Y1 - 2022/10/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-21-4277
DO - 10.1158/0008-5472.CAN-21-4277
M3 - Article
C2 - 36166646
AN - SCOPUS:85140144394
SN - 0008-5472
VL - 82
SP - 3802
EP - 3814
JO - Cancer Research
JF - Cancer Research
IS - 20
ER -