Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival

EBioMedicine. 2016 Jun:8:150-158. doi: 10.1016/j.ebiom.2016.05.009. Epub 2016 May 7.

Abstract

SCRIB is a polarity regulator known to be abnormally expressed in cancer at the protein level. Here we report that, in breast cancer, an additional and hidden dimension of deregulations exists: an unexpected SCRIB exon usage pattern appears to mark a more malignant tumor phenotype and significantly correlates with survival. Conserved exons encoding the leucine-rich repeats tend to be overexpressed while others are underused. Mechanistic studies revealed that the underused exons encode part of the protein necessary for interaction with Vimentin and Numa1, a protein which is required for proper positioning of the mitotic spindle. Thus, the inclusion/exclusion of specific SCRIB exons is a mechanistic hallmark of breast cancer, which could potentially be exploited to develop more efficient diagnostics and therapies.

Keywords: Breast cancer; Mitosis; Polarity; SCRIB; Splicing; Survival.

MeSH terms

  • Alternative Splicing*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Polarity / genetics
  • Cluster Analysis
  • Exons*
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • HEK293 Cells
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Mitosis / genetics
  • Phenotype
  • Prognosis
  • Protein Interaction Domains and Motifs
  • Tumor Suppressor Proteins / chemistry
  • Tumor Suppressor Proteins / genetics*

Substances

  • Membrane Proteins
  • SCRIB protein, human
  • Tumor Suppressor Proteins