Abstract 3560: IFITM1 overexpression enhances the aggressive phenotype of inflammatory breast cancer in a STAT2-dependent manner

Inflammatory breast cancer (IBC) is a highly metastatic, aggressive, and fatal form of breast cancer that accounts for about 1 to 5% of all breast cancers diagnosed in the United States. At present, the molecular mechanisms that underlie the aggressive phenotype of IBC are not known. Interferon induced transmembrane protein1 (IFITM1) is a member of interferon stimulated genes (ISGs), whose overexpression has been linked to several malignancies, but its role in inflammatory breast cancer is not known. The primary role of IFITM1 is to stop the spread of viral pathogens in the host's cells, but its constitutive overexpression has been shown to enhance malignancy. IFITM1 expression is known to be regulated by type 1 interferon through activation of the canonical JAK-STAT pathway; however, recent studies suggest that non-canonical signaling pathways involving STAT2 homodimers can also regulate IFITM1 expression. In the present study, we determined whether IFITM1 plays a critical role in driving the aggressive phenotype of three IBC cell lines; SUM149; MDA-IBC-3, and SUM190.Western blot and RT-PCR analyses indicated that IFITM1 was constitutively overexpressed at the protein (∼5- to 10-fold) and mRNA (∼4-fold) level, respectively, in SUM149 and MDA-IBC-3 cells but not expressed in non-IBC MCF-7 luminal breast cancer cells, and that its overexpression strongly correlated with increased proliferation, migration and invasion, and enhanced colony formation.Notably, the aggressive p...
Source: Cancer Research - Category: Cancer & Oncology Authors: Tags: Experimental and Molecular Therapeutics Source Type: research