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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0443-5) contains supplementary material, which is available to authorized users.
Highlights
Mammary gland development is the result of coordinated actions of hormones, growth factors and extracellular matrix signalling pathways
Activating mutations in the Ras or phosphoinositide 3-kinase (PI3K) pathway do not overcome the requirement of a functional p130Cas/focal adhesion kinase (FAK) signalling complex for the survival and growth of human breast cancer cells [17]
This study revealed that depletion of Nedd9 impairs mammary tumour development by limiting the activation of multiple pro-oncogenic signalling proteins, including its binding partners Fak and Src as well as Ras downstream effectors
Summary
Mammary gland development is the result of coordinated actions of hormones, growth factors and extracellular matrix signalling pathways. These indications for p130Cas having a role as a positive regulator of mammary cell growth are strengthened by the fact that in vivo over-expression of p130Cas/BCAR1 causes extensive hyperplasia throughout mammary gland development, delayed involution at the end of lactation, along with persistent proliferation, decreased apoptosis and hyper-activation of Src, Erk1/2 and Akt signalling pathways [3].
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