The p140Cap adaptor protein as a molecular hub to block cancer aggressiveness

Cell Mol Life Sci. 2021 Feb;78(4):1355-1367. doi: 10.1007/s00018-020-03666-w. Epub 2020 Oct 20.

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: Chromosome 17q12; Gene amplification; Interactome analysis; Metastasis; SRCIN1; miRNA.

Publication types

  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Vesicular Transport / genetics*
  • Animals
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinogenesis / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Mice
  • Neoplasm Metastasis
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Receptor, ErbB-2 / genetics
  • Signal Transduction / genetics

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • SRCIN1 protein, human
  • ERBB2 protein, human
  • Receptor, ErbB-2