The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness
- PDF / 3,175,179 Bytes
- 13 Pages / 595.276 x 790.866 pts Page_size
- 19 Downloads / 153 Views
Cellular and Molecular Life Sciences
REVIEW
The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness Vincenzo Salemme1 · Costanza Angelini1 · Jennifer Chapelle1 · Giorgia Centonze1 · Dora Natalini1 · Alessandro Morellato1 · Daniela Taverna1 · Emilia Turco1 · Ugo Ala2 · Paola Defilippi1 Received: 18 May 2020 / Revised: 3 September 2020 / Accepted: 5 October 2020 © The Author(s) 2020
Abstract The 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. Keywords SRCIN1 · Metastasis · Chromosome 17q12 · Gene amplification · miRNA · Interactome analysis Abbreviations SRCIN1 Src Kinase Signaling Inhibitor 1 p140Cap Cap: p130Cas-associated protein BC Breast cancer NB Neuroblastoma
Vincenzo Salemme, Costanza Angelini, and Jennifer Chapelle contributed equally to this work * Ugo Ala [email protected] * Paola Defilippi [email protected] 1
Department of Molecular Biotechnology and Health Science, Università degli Studi di Torino, Via Nizza 52, 10126 Torino, Italy
Department of Veterinary Sciences, Università degli Studi di Torino, Largo Paolo Braccini 2, 10095 Grugliasco, TO, Italy
2
Introduction p140Cap, also known as p130Cas-associated protein or SNIP (SNAP-25 Interacting Protein), is a scaffold molecule involved in the formation of multi-protein complexes [1–4]. The p140Cap protein is encoded by the Src Kinase Signaling Inhibitor 1 gene (SRCIN1), located on chromosome 17q12 [4]. Structurally, p140Cap is a highly hydrophilic protein, which does contain neither a signal sequence nor a putative transmembrane domain [1]. Its amino acid sequence includes a tyrosine-rich domain, a putative actin-binding site, two proline-rich domains containing multiple PPXY and PXXP involved in protein–protein interactions with the SH3 domains, a coil-coiled region and two C-terminal highly charged regions [1, 3]. Furthermore, p140Cap includes several serine,
Data Loading...
