p130Cas/BCAR1 and p140Cap/SRCIN1 Adaptors: The Yin Yang in Breast Cancer?

Abstract

p130Cas/BCAR1 is an adaptor protein devoid of any enzymatic or transcriptional activity, whose modular structure with various binding motifs, allows the formation of multi-protein signaling complexes. This results in the induction and/or maintenance of signaling pathways with pleiotropic effects on cell motility, cell adhesion, cytoskeleton remodeling, invasion, survival, and proliferation. Deregulation of p130Cas/BCAR1 adaptor protein has been extensively demonstrated in a variety of human cancers in which overexpression of p130Cas/BCAR1 correlates with increased malignancy. p140Cap (p130Cas associated protein), encoded by the SRCIN1 gene, has been discovered by affinity chromatography and mass spectrometry analysis of putative interactors of p130Cas. It came out that p140Cap associates with p130Cas not directly but through its interaction with the Src Kinase. p140Cap is highly expressed in neurons and to a lesser extent in epithelial tissues such as the mammary gland. Strikingly, in vivo and in vitro analysis identified its tumor suppressive role in breast cancer and in neuroblastoma, showing an inverse correlation between p140Cap expression in tumors and tumor progression. In this review, a synopsis of 15 years of research on the role of p130Cas/BCAR1 and p140Cap/SRCIN1 in breast cancer will be presented.

Creatine kinase brain-type regulates BCAR1 phosphorylation to facilitate DNA damage repair

“…We obtained total of 10 proteins as positive hits from the phosphoproteomics data ( Figure 1 E) ( Data S1 ). Among these proteins, BCAR1 (p130Cas), as an adaptor protein mediating multiple signaling pathways to modulate cell motility, cell cycle, cell transformation, and apoptosis, 21 , 22 , 23 , 24 was selected for further validation.…”

p140Cap modulates the mevalonate pathway decreasing cell migration and enhancing drug sensitivity in breast cancer cells

“…There is emerging interest in exploiting statins in anticancer therapy, since there is preclinical evidence of their antiproliferative, proapoptotic, and anti-invasive properties [ 65 – 67 ]. Moreover, clinical data on BC patient cohorts show that statins can reduce the percentage of patients who experience relapse after therapy and thereby increase BC survival [ 18 , 19 ].…”

SRC kinase-mediated signaling pathways and targeted therapies in breast cancer

“…In addition, activated SRC/FAK module can further activate multiple other FA components to initiate a cascade of signal transduction events that regulate BC tumorigenesis and metastasis [ 66 – 68 ]. These FA components that have been reported in BC include Paxillin [ 69 , 70 ], Tensin-3 [ 71 ], TKS5 [ 72 ], CAV-1 [ 73 , 74 ], LPP [ 75 ], p130Cas [ 76 ] and p190RhoGAP [ 77 – 79 ] (Fig. 4 and Table 1 ).…”