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Review
. 2014;16(5):443.
doi: 10.1186/s13058-014-0443-5.

Cas proteins: dodgy scaffolding in breast cancer

Giusy Tornillo  1 , Paola Defilippi, Sara Cabodi
Affiliations
Review

Cas proteins: dodgy scaffolding in breast cancer

Giusy Tornillo et al. Breast Cancer Res. 2014.

Abstract

The members of the Cas protein family (p130Cas/BCAR1, Nedd9/HEF1, EFS and CASS4) are scaffold proteins required for the assembly of signal transduction complexes in response to several stimuli, such as growth factors, hormones and extracellular matrix components. Given their ability to integrate and coordinate multiple signalling events, Cas proteins have emerged as crucial players in the control of mammary cell proliferation, survival and differentiation. More importantly, it has been found that alterations of their expression levels result in aberrant signalling cascades, which promote initiation and progression of breast cancer. Based on the increasing data from in vitro, mouse model and clinical studies, in this review we will focus on two Cas proteins, p130Cas/BCAR1 and Nedd9, and their coupled signalling pathways, to examine their role in mammary cell transformation and in the acquirement of invasiveness and drug resistance of breast cancer cells.

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Figures

Figure 1
Figure 1
p130Cas/BCAR1 and Nedd9 structural features and main interacting proteins. Schematic representation of Cas protein main domains: an amino-terminal SH3 domain followed by a proline-rich region (PRR), a substrate domain (SD), a serine rich region (SRR), and a carboxy-terminal domain (CT). The main proteins whose interaction has been demonstrated for both p130Cas and Nedd9 are indicated in black, the interactors specific for p130Cas are in red and those specific for Nedd9 are in green. Noteworthy, p125FAK binds to the SH3 domain while the Src family kinases bind to the CT domain. The substrate domain with the multiple YxxP motifs represents the site where Src family kinases extensively phosphorylate Cas proteins.
Figure 2
Figure 2
Schematic representation of the mechanisms of Aurora-A kinase regulation by Nedd9 and major effects of Nedd9 up-regulation mediated by Aurora-A kinase in breast cancer cells. AurA, Aurora-A; CTTN, cortactin; Ub, ubiquitin.
Figure 3
Figure 3
Biological effects and signalling pathways involving p130Cas/BCAR1 and Nedd9 in different breast cancer subtypes. (A) Estrogen receptor (ER)-positive breast cancer. (B) ErbB2-positive breast cancer. (C) Triple-negative breast cancer. PI3K, phosphoinositide 3-kinase; SRF, serum response factor; TGF, transforming growth factor.
Figure 4
Figure 4
Schematic representation of the mechanisms underlying p130Cas/BCAR1 up-regulation in tamoxifen-resistant cells and major signalling events in p130Cas/BCAR-dependent anti-oestrogen resistance. PI3K, phosphoinositide 3-kinase; SD, substrate domain.
See this image and copyright information in PMC

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