Abstract
AbstractThe p140Cap adaptor protein is a scaffold molecule encoded by the SRCIN1 gene, which is physiologically expressed in several epithelial tissues and in the neurons. However, p140Cap is also strongly expressed in a significant subset of cancers including breast cancer and neuroblastoma. Notably, cancer patients with high p140Cap expression in their primary tumors have a lower probability of developing a distant event and ERBB2-positive breast cancer sufferers show better survival. In neuroblastoma patients, SRCIN1 mRNA levels represent an independent risk factor, which is inversely correlated to disease aggressiveness. Consistent with clinical data, SRCIN1 gain or loss of function mouse models demonstrated that p140Cap may affect tumor growth and metastasis formation by controlling the signaling pathways involved in tumorigenesis and metastatic features. This study reviews data showing the relevance of SRCIN1/p140Cap in cancer patients, the impact of SRCIN1 status on p140Cap expression, the specific mechanisms through which p140Cap can limit cancer progression, the molecular functions regulated by p140Cap, along with the p140Cap interactome, to unveil its key role for patient stratification in clinics.
Funder
Associazione Italiana Ricerca cancro
Fondazione Cassa Risparmio Torino
Associazione Italiana per la Ricerca sul Cancro
Università degli Studi di Torino
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Cellular and Molecular Neuroscience,Pharmacology,Molecular Biology,Molecular Medicine
Reference87 articles.
1. Chin LS, Nugent RD, Raynor MC, Vavalle JP, Li L (2000) SNIP, a novel SNAP-25-interacting protein implicated in regulated exocytosis. J Biol Chem 275(2):1191–1200. https://doi.org/10.1074/jbc.275.2.1191
2. Cabodi S, del Pilar C-L, Di Stefano P, Defilippi P (2010) Integrin signalling adaptors: not only figurants in the cancer story. Nat Rev Cancer 10(12):858–870. https://doi.org/10.1038/nrc2967
3. Di Stefano P, Cabodi S, Boeri Erba E, Margaria V, Bergatto E, Giuffrida MG, Silengo L, Tarone G, Turco E, Defilippi P (2004) P130Cas-associated protein (p140Cap) as a new tyrosine-phosphorylated protein involved in cell spreading. Mol Biol Cell 15(2):787–800. https://doi.org/10.1091/mbc.e03-09-0689
4. Di Stefano P, Leal MP, Tornillo G, Bisaro B, Repetto D, Pincini A, Santopietro E, Sharma N, Turco E, Cabodi S, Defilippi P (2011) The adaptor proteins p140CAP and p130CAS as molecular hubs in cell migration and invasion of cancer cells. Am J Cancer Res 1(5):663–673
5. Repetto D, Aramu S, Boeri Erba E, Sharma N, Grasso S, Russo I, Jensen ON, Cabodi S, Turco E, Di Stefano P, Defilippi P (2013) Mapping of p140Cap phosphorylation sites: the EPLYA and EGLYA motifs have a key role in tyrosine phosphorylation and Csk binding, and are substrates of the Abl kinase. PLoS ONE 8(1):e54931. https://doi.org/10.1371/journal.pone.0054931
Cited by
7 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献