Dosage-dependent regulation of VAV2 expression by steroidogenic factor-1 drives adrenocortical carcinoma cell invasion

摘要: Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with dismal prognosis. Genomic studies have enabled progress in our understanding of the molecular bases ACC, but factors that influence its prognosis are lacking. Amplification gene encoding transcription factor steroidogenic factor-1 (SF-1; also known as NR5A1) one genetic alterations common ACC. We identified transcriptional regulatory mechanism involving increased abundance VAV2, guanine nucleotide exchange for small GTPases control cytoskeleton, driven by expression SF-1 Manipulating and VAV2 cultured ACC cells revealed was critical SF-1–induced cytoskeletal remodeling invasion culture (Matrigel) vivo (chicken chorioallantoic membrane) models. Analysis patient cohorts indicated greater robustly correlated poor patients. Because druggable target, findings suggest blocking may be new therapeutic approach to inhibit metastatic progression