NIH Research Festival
Inflammation and hypoxia are strongly linked to cancer progression. Hypoxia and inflammatory cytokines like IL-6 signal in part through the transcription factor C/EBPD, which drives mesenchymal features and malignant progression of glioblastoma. Here we report a different role for C/EBPD in breast cancer. Previous studies in MMTV-Neu transgenic mice revealed contrasting functions of C/EBPD in reducing mammary tumor multiplicity while promoting metastasis. This study shows that the C/EBPD protein is expressed in normal breast and low-grade oestrogen receptor positive (ER+) cancers, and correlates with longer progressionfree survival of breast cancer patients. Functional studies in cell lines show that ERα promotes C/EBPD protein stability, and that C/EBPD attenuates cell growth, motility and invasiveness by inhibiting expression of the SNAI2 (Slug) transcriptional repressor, leading to expression of CDKN1A (p21CIP1/WAF1). Expression of CEBPD but not CEBPB mRNA in combination with IL6 correlates with lower risk of progression in ER+ breast cancer patients. These findings indicate that C/EBPD attenuates progression of ER+ breast cancer and support a potentially beneficial role for the IL-6 pathway in ER+ breast cancer.
Scientific Focus Area: Cancer Biology
This page was last updated on Friday, March 26, 2021