WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple‐negative breast cancer via NF‐κB activation

Abstract

WBP2 promotes BTRC mRNA stability to drive migration and invasion in triple-negative breast cancer via NFB activation

Reciprocal Regulation of Hippo and WBP2 Signalling—Implications in Cancer Therapy

“…In line with these clinical studies, WBP2 has been reported to be frequently amplified or gained in multiple breast cancer databases including TCGA BRCA and METABRIC datasets [65]. Functionally, WBP2 has been found to promote several cancer phenotypes including growth [61,64,66], cell cycle progression [67], migration [61,68], invasion [61,62,68], epithelial mesenchymal transition [61] and chemotherapeutic resistance [64,67,69] in a number of breast cancer cell lines.…”

“…Strategies to Limit WBP2 Expression at Post-Translational Levels Aberrations of WBP2 not only occur at its mRNA level, but also at its protein level. An integrated proteogenomic analysis performed on breast, ovarian and colorectal cancers demonstrated only a low or moderate correlation between WBP2 mRNA and protein expression [68]. Furthermore, an analysis of WBP2 protein-mRNA correlation over a panel of 17 breast cancer cell lines revealed only a partial concordance of approximately 50% [62].…”

“…Several meta-analyses have illustrated the association between WBP2 and the integrin signalling pathway in the TCGA BRCA dataset [54,68]. Furthermore, a mass spectrometry analysis performed on glioma cells also identified VASP to be a putative binding partner of WBP2 [74].…”

“…Although not fully clarified, we conceive that this regulatory mechanism is likely to be through WBP2-mediated MPC activity. The induction of BTRC by WBP2 resulted in increased IκBα ubiquitin-mediated proteasomal degradation, and consequently NFκB activity, in turn driving TNBC migration and invasion [68].…”

“…To obtain a more comprehensive view of WBP2 in cancer, our meta-analysis based on the TCGA Pan-Cancer Atlas revealed that WBP2 amplification was observed at high frequencies in approximately 78% of 32 cancer types (Figure 4) [68]. These include hepatocellular carcinoma, non-small cell lung cancer, glioma and gastric cancer [70][71][72], where WBP2 has already been reported to be functionally implicated.…”