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

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

Author information

1
School of Biological Sciences, University of Essex, CO4 3SQ, United Kingdom.
2
Department of Mathematical Sciences, University of Essex, CO4 3SQ, United Kingdom.
3
School of Biological Sciences, University of Essex, CO4 3SQ, United Kingdom. Electronic address: mmetod@essex.ac.uk.

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

PMID:
27428426
PMCID:
PMC4919504
DOI:
10.1016/j.ebiom.2016.05.009
[Indexed for MEDLINE]
Free PMC Article

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