GSE112910
FRY Impacts Breast Cancer Malignancy by Inducing an Enrichment of Genes with Tumor-Suppressive Functions and Affecting EMT Potential of Breast Cancer Cells
Breast cancer is a disease with diverse phenotypes, and while the progression of breast cancer from a localized lesion to metastatic disease is well understood clinically. Our previous study genetically linked the FRY gene with differential susceptibility to mammary carcinogenesis; however, little is known about the mechanistic insights of FRY in mammalian cells and breast cancer progression. Through RNA-Seq analysis of series of constructed cell lines based on highly malignant triple-negative human breast cancer cells MDA-MB-231, we show that enhanced FRY induces massive changes in gene expression, which favor signalings and molecules with tumor-suppressive functions and engage in promoting cell differentiation, maintaining the normal and histopathological characteristics of epithelial cells, and in regulating EMT potential of breast cancer cells. As a result, the proliferation, migration and invasion potentials of breast cancer cells are significantly inhibited both in vitro and in xenograft tumor models. Importantly, consistent with FRY's anti-tumor progression role, decreased FRY protein levels are correlated with poorly differentiated and aggressive tumor phenotypes in the analysis of two clinically annotated breast cancer cohorts. Our results identify FRY's potent tumor-suppressive role at the gene transcription and molecular function levels, providing a novel biomarker for breast cancer prognosis and a target for therapeutic intervention. Overall design: Examination of two repeats for parental, vector-ctrl and FRY expressing MDA-MB-231 cells.