Breast cancer anti-estrogen resistance 3 (BCAR3)

Breast cancer anti-estrogen resistance 3 (BCAR3) is a signaling adaptor protein that plays a critical role in the development of resistance to anti-estrogen therapies, such as tamoxifen, in breast cancer patients [1, 4]. It contains an SH2 domain and a C-terminal CDC25-like guanine nucleotide exchange factor (GEF) domain, which allow it to mediate protein-protein interactions and regulate intracellular signaling pathways [1, 5]. BCAR3 primarily functions by binding to BCAR1 (also known as p130Cas), leading to the activation of downstream effectors like Rac1, Cdc42, and Src kinase, which promote cell proliferation, survival, and increased motility [3, 5]. In clinical settings, overexpression of BCAR3 is frequently associated with poor prognosis and the progression of estrogen receptor-positive breast cancers to an endocrine-resistant state [4]. Beyond its role in breast cancer, BCAR3 is involved in the invasive and metastatic potential of various other solid tumors by modulating cytoskeletal dynamics [5]. While there are currently no FDA-approved drugs that directly target BCAR3, it is considered a high-priority target for developing novel therapeutics to overcome drug resistance and inhibit cancer metastasis [4, 5]. Sources: [1] UniProt (O75186); [2] NCBI Gene (8412); [3] van Agthoven et al. (1998) EMBO J; [4] Schrecengost et al. (2015) Mol Cancer Res; [5] Wilson et al. (2019) Cancer Res.

Other names

SH2 domain-containing protein 3BSH2D3BNovel SH2-containing protein 2NSP2Breast cancer anti-estrogen resistance protein 3

Disruption of BCAR3-p130Cas protein-protein interaction and inhibition of BCAR3-mediated GEF activity to restore anti-estrogen sensitivity.