title: Decreased Usage of Specific Scrib Exons Defines a More Malignant Phenotype of Breast Cancer With Worsened Survival.
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.
authors.affiliation: School of Biological Sciences, University of Essex, CO4 3SQ, United Kingdom.
authors.forename: Gergana
authors.initials: G
authors.lastname: Metodieva
authors.affiliation: School of Biological Sciences, University of Essex, CO4 3SQ, United Kingdom.
authors.forename: Samson
authors.initials: S
authors.lastname: Adoki
authors.affiliation: Department of Mathematical Sciences, University of Essex, CO4 3SQ, United Kingdom.
authors.forename: Berthold
authors.initials: B
authors.lastname: Lausen
authors.affiliation: School of Biological Sciences, University of Essex, CO4 3SQ, United Kingdom. Electronic address: mmetod@essex.ac.uk.
authors.forename: Metodi V
authors.initials: MV
authors.lastname: Metodiev
mesh_terms: D017398:Alternative Splicing; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D002460:Cell Line; D016764:Cell Polarity / Q000235:genetics; D016000:Cluster Analysis; D005091:Exons; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D008938:Mitosis / Q000235:genetics; D010641:Phenotype; D011379:Prognosis; D054730:Protein Interaction Domains and Motifs; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics*
chemical_list: D008565:Membrane Proteins; C480591:SCRIB protein, human; D025521:Tumor Suppressor Proteins
keywords: Breast cancer; Mitosis; Polarity; SCRIB; Splicing; Survival