Bcar1, also known as p130Cas/BCAR1, is an adaptor protein belonging to the CAS family of scaffold proteins [3]. It lacks enzymatic or transcriptional activity but its modular structure with various binding motifs enables the formation of multi-protein signaling complexes. This leads to the induction and/or maintenance of signaling pathways that have pleiotropic effects on cell motility, adhesion, cytoskeleton remodeling, invasion, survival, and proliferation [1]. It is involved in signaling originating from mechanical stimuli, cell-extracellular matrix adhesion, and growth factor stimulation cascades [3].

Bcar1 constitutive knockout mice are embryonic lethal by embryonic days (E)11.5-12.5 [4]. Conditional knockout of Bcar1 in SM22-expressing smooth muscle cells and cardiac tissues was embryonically lethal from E14.5-15.5 due to severe cardiovascular defects, including abnormal ventricular development and failure of outflow tract septation [4]. Knockout of Bcar1 specifically in neural crest cells recapitulated part of the outflow tract septation and aortic sac defects, indicating a cell-specific requirement for Bcar1 in these cells for outflow tract septation [4]. In zebrafish, bcar1-/-zebrafish failed to form the caudal vein plexus, with endothelial cells showing fewer filopodial structures and inefficient detachment from neighboring cells [6]. In cancer, knockdown of BCAR1 in lung adenocarcinoma cells inhibited proliferation, colony formation, cell invasion, and migration, and prohibited tumor formation in nude mice [5,7]. In gastric cancer, BCAR1 knockdown blocked FLOT1-induced cell proliferation, migration, and invasion [2].

In conclusion, Bcar1 is essential for various biological processes, especially in cardiovascular development, angiogenesis, and in the context of cancer progression. The use of gene knockout and conditional knockout mouse models, as well as zebrafish models, has significantly enhanced our understanding of Bcar1's role in these specific disease-related biological processes.