Apr 19, 2020

PRP4K is a haploinsufficient tumour suppressor negatively regulated during epithelial-to-mesenchymal transition

BioRxiv : the Preprint Server for Biology
L. E. ClarkeGraham Dellaire

Abstract

Reduced expression of haploinsufficient tumour suppressor genes is sufficient to alter cellular phenotypes towards carcinogenesis without complete loss of gene expression. As an essential gene, complete expression loss of pre-mRNA processing factor 4 kinase (PRP4K, also known as PRPF4B) is lethal. However, we demonstrate here that reduction of PRP4K levels by small interfering RNA in the mammary epithelial cell lines HMLE and MCF10A can induce partial epithelial-to-mesenchymal transition (EMT) marked by the retention of epithelial markers such as Zo-1 and E-cadherin, and upregulation of mesenchymal markers such as fibronectin and Zeb1. This partial EMT phenotype in non-transformed PRP4K-depleted cells is associated with greater invasive potential in 3D transwell assays, but either reduces or has no effect on 2D migration examined by scratch assay. This is in contrast to depletion of PRP4K in transformed triple-negative MDA-MB-231 breast cancer cells, which results in enhanced migration in 2D and invasion in 3D. Induction of EMT, using EMT-inducing media containing WNT-5a and TGF-{beta}1 or depletion of eukaryotic translation initiation factor 3e (eIF3e) by shRNA, results in marked reduction of PRP4K expression. EMT induced by e...Continue Reading

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Mentioned in this Paper

HSPA6
HSPA6 gene
HBEGF
Heat-Shock Proteins 70
Trophoblast Cell
Placentation
Genes
Matrix Metalloproteinase 2 Measurement
Transcription, Genetic
Metalloendopeptidase Activity

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