Breast cancer anti-estrogen resistance protein 3 (BCAR3) (BCAR3)

Breast cancer anti-estrogen resistance protein 3 (BCAR3), also known as SH2D3B or NSP2, is a scaffold protein that plays a critical role in mediating resistance to anti-estrogen therapies, such as tamoxifen, in breast cancer (UniProt Q9Y2S2; PMID: 10467404). It functions primarily as an adaptor protein, utilizing its SH2 domain and GEF-like domain to interact with other signaling molecules like p130Cas (BCAR1) and PTPN13 (PMID: 21167771). These interactions activate downstream pathways involving Src, focal adhesion kinase (FAK), and Rho GTPases, which promote cell proliferation, survival, and increased motility (PMID: 25403711). Beyond its role in oncology, genetic variants in the BCAR3 gene have been strongly associated with Paget's disease of bone, suggesting a role in osteoclast function and bone remodeling (NCBI Gene 8412; PMID: 21167771). As a therapeutic target, BCAR3 is of interest for overcoming endocrine resistance in ER-positive breast cancers, though no specific small-molecule inhibitors are currently in clinical use. Targeting BCAR3 mRNA via antisense oligonucleotides or siRNA represents a potential strategy to downregulate its expression and restore drug sensitivity in resistant tumors.

Other names

SH2 domain-containing protein 3BSH2D3BNovel SH2-containing protein 2NSP2

Downregulation of BCAR3 expression via RNA interference or antisense oligonucleotides to inhibit downstream signaling pathways.