ARRDC3 suppresses breast cancer progression by negatively regulating integrin β4

摘要: Large-scale genetic analyses of human tumor samples have been used to identify novel oncogenes, suppressors and prognostic factors, but the functions molecular interactions many individual genes not determined. In this study we examined cellular effects mechanism arrestin family member, ARRDC3, a gene preferentially lost in subset breast cancers. Oncomine data revealed that expression ARRDC3 decreases with grade, metastases recurrences. overexpression represses cancer cell proliferation, migration, invasion, growth soft agar vivo tumorigenicity, whereas downregulation ARRCD3 has opposite effects. Mechanistic studies showed regulatory pathway controls surface adhesion molecule, β-4 integrin (ITGβ4), protein associated aggressive behavior. Our indicates directly binds phosphorylated form ITGβ4 leading its internalization, ubiquitination ultimate degradation. The results ARRCD3-ITGβ4 as new therapeutic target show importance connecting arrays mechanistic search for treatments.