Haploinsufficient tumor suppressor PRP4K is negatively regulated during epithelial‐to‐mesenchymal transition

Abstract

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Tinker, Tailor, Tumour Suppressor: The Many Functions of PRP4K

“…CTGF, CRY61, ANKRD1 and AJUBA) ( Figure 4 ). Similarly, Clarke et al (2021) found that PRP4K knockdown promotes transformed breast cancer cell migration and invasion, yet appeared to inhibit 2D cell migration in non-transformed MCF10A cells. Thus, transformation state of the cell may play an important role in physiological outcome of PRP4K depletion in regard to enhanced cell migration and invasion.…”

“…Several studies have now demonstrated that PRP4K regulation of YAP is a conserved process between flies and mammals ( Cho et al, 2018 ; Clarke et al, 2021 ; Zhou et al, 2021 ). For example, Clarke et al (2021) showed that when EMT was induced by media containing transforming growth factor beta (TGFβ) or as a result of EIF3E loss in the non-transformed mammary cell line MCF10A, PRP4K expression was reduced ( Figure 4 ), and this correlated with increased YAP nuclear translocation and target gene expression in EIF3E-depleted MCF10A cells.…”

“…Several studies have now demonstrated that PRP4K regulation of YAP is a conserved process between flies and mammals ( Cho et al, 2018 ; Clarke et al, 2021 ; Zhou et al, 2021 ). For example, Clarke et al (2021) showed that when EMT was induced by media containing transforming growth factor beta (TGFβ) or as a result of EIF3E loss in the non-transformed mammary cell line MCF10A, PRP4K expression was reduced ( Figure 4 ), and this correlated with increased YAP nuclear translocation and target gene expression in EIF3E-depleted MCF10A cells. Intriguingly, activation of Yap signaling seemed to occur as a result of PRP4K loss, since the addback of PRP4K in EIF3E-depleted cells led to increased YAP shuttling to the cytoplasm and reduced YAP target gene expression.…”

“…As such, this may represent an important physiological regulatory mechanism controlling Yap signaling during liver and intestinal regeneration ( Zhou et al, 2021 ). However, in malignant cells, aberrant Yap signaling is associated with increased tumour cell growth, migration, and invasion ( Cho et al, 2018 ; Clarke et al, 2021 ). Cho et al (2018) found that PRP4K knockdown promotes breast cancer cell growth and invasion, in part facilitated by the increased activation of YAP target genes (e.g.…”

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook

“…AKR1B10 downregulated CDH1 expression via the PI3K/AKT/NF-κB p65 signaling pathway in MCF-7 cells ( 113 ). Moreover, taxane therapy resistance was related to reduced PRP4K expression, depletion of PRP4K in TNBC cells (MDA-MB-231), and enhanced 2D migration, and 3D invasion correlated with higher fibronectin levels rather than changes in CDH1 ( 114 ). Connexins linked to N-cadherin, vimentin, Snail, and Zeb1 modulate CSC and EMT properties in breast cancer cells ( 90 ).…”