BCAR scaffold protein, Cas family member | Elisa - Clia - Antibody - Protein

Background

BCAR1 (Breast Cancer Anti-Estrogen Resistance Protein 1), also known as p130Cas (Crk-associated substrate), is a signaling protein that plays a pivotal role in various cellular processes such as migration, invasion, survival, and proliferation. Originally identified in a screen for genes that confer resistance to anti-estrogen therapy in breast cancer, BCAR1 has since been implicated in a variety of cancers and other diseases. Its expression is ubiquitous but particularly pronounced in tissues with high cellular turnover and in metastatic cancers, highlighting its role in dynamic cellular environments.

Protein Structure

BCAR1 is a multidomain scaffolding protein that integrates signals from various pathways:

• SH3 Domain: Located at the N-terminus, the Src Homology 3 (SH3) domain mediates interactions with proline-rich sequences in other proteins.
• Multiple Substrate Domains: These include a large number of tyrosine residues that can be phosphorylated, creating binding sites for SH2 domain-containing proteins.
• CCHD (C-terminal Cas family homology domain): Important for protein-protein interactions and localization within the cell.
• Proline-Rich Regions: These facilitate binding to SH3 domain-containing proteins, thus mediating various signal transduction processes.

Classification and Subtypes

BCAR1 belongs to the Cas (Crk-associated substrate) family of scaffold proteins, which are characterized by their role in cellular signaling and structure. Other members of this family include Efs/Sin and HEF1/NEDD9/Cas-L, which share structural and functional similarities with BCAR1.

Function and Biological Significance

BCAR1 functions as a central hub in various signaling pathways:

• Cell Migration and Invasion: By interacting with integrins and other components of the extracellular matrix, BCAR1 facilitates cell movement and invasion, which are critical processes in cancer metastasis.
• Cell Survival and Proliferation: Through its interactions with focal adhesion kinase (FAK) and Src kinases, BCAR1 promotes cell survival and proliferation, helping cells to evade apoptosis.
• Anti-Estrogen Resistance: In breast cancer, BCAR1 is crucial in mediating resistance to anti-estrogen therapies such as tamoxifen, through its ability to activate downstream signaling pathways independent of estrogen receptor signaling.

Clinical Issues

BCAR1 is implicated in several clinical contexts:

• Cancer: Elevated BCAR1 expression is associated with poor prognosis in various cancers, including breast, lung, and ovarian cancers. It is often linked with increased metastatic potential and resistance to therapy.
• Therapeutic Target: Given its role in cancer progression and therapy resistance, BCAR1 is a potential target for new cancer therapies. Inhibiting its function could restore sensitivity to existing treatments and reduce metastatic spread.
• Biomarker: BCAR1 levels can serve as a biomarker for the aggressiveness of certain cancers and their likelihood of responding to specific treatments.

Summary

BCAR1 is a multifunctional scaffold protein integral to numerous cellular processes, particularly those involving migration, invasion, and survival. Its prominent role in conferring resistance to anti-estrogen therapies in breast cancer underscores its clinical significance. Understanding the intricate network of interactions and pathways mediated by BCAR1 can provide insights into new therapeutic strategies for combating resistant and metastatic cancers.