Mechanistically, we found that RKIP overexpression led to down-regula- tion of the NF-kB signaling pathway and inhibition of the epithelial-to-mesenchymal transition, which is important step for cancer metastasis.
This reduction, or loss of expression, is correlated not only with the presence of metastasis, contributing to RKIP's classification as a metastasis suppressor, but also with tumour aggressiveness and poor prognosis.
Accumulating evidence has indicated that Raf kinase inhibitor protein (RKIP) is involved in several intracellular signaling pathways; its abnormal expression is associated with tumor progression and metastasis in several human neoplasms.
In conclusion, our studies demonstrate how KRAS inhibits the tumor suppressor RKIP, thus offering novel justification for targeting RKIP as a strategy to overcome KRAS-induced tumor metastasis and chemoresistance in PDAC.
In particular, the loss of RKIP's function in certain types of cancer cells results in epithelial to mesenchymal transition (EMT) and the promotion of cancer metastasis.
We further provide updated justification for targeting RKIP as a strategy to overcome tumor chemo/immuno-resistance and suppress metastasis, through the use of agents able to modulate RKIP expression in cancer cells.
In this review, we summarize our current understanding of RKIP regulation in tumors and consider experimental and computational strategies for recovering or mimicking its function by targeting mediators of metastasis.
Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo.
Raf kinase inhibitor protein (RKIP) appears to control cancer cell metastasis and its expression in colonic tissue is related to colonic cancer development.
The cytoprotective effect of PDT-induced NO is observed at low NO levels, which activate the pro-survival/anti-apoptotic NF-κB and YY1, while inhibiting the anti-survival/pro-apoptotic and metastasis suppressor RKIP.
We carried out proteomics analysis of 93 urinary samples of healthy subjects (HS) and patients affected by ccRCC, prostate cancer (PCa) and chronic kidney disease (CKD), that was able to successfully distinguish each group.The most significant candidate biomarker was identified by mass spectrometry as Raf Kinase Inhibitor Protein (RKIP), a key regulator of cell signaling, already described in several cancer types as a metastasis suppressor.
Chiefly, these findings suggest that targeted inhibition of YY1 by specific small molecule inhibitors and/or the specific induction of RKIP expression and activity are potential therapeutic strategies to block tumor growth and metastasis in many cancers, as well as to overcome anticancer drug resistance.
Hence, the activities of Raf-kinase inhibitor protein contrast, in part, to those mediated by several cancer stem cell transcription factors for their roles in resistance and metastasis.
We used species-specific RNA sequencing in a mouse xenograft model to determine how the metastasis suppressor RKIP influences transcription in a panel of paired tumor and stroma tissues.
Our study implies that detection of Bmi-1 and RKIP is valuable in predicting patient survival and therapeutic response in gastric cancer, and the inverse association between Bmi-1 and RKIP reveals the potential molecular mechanisms underlying tumor metastasis and chemotherapy resistance.
Here, we establish a novel pathway for RKIP regulation of metastasis inhibition through the negative regulation of RANTES/CCL5 thereby limiting tumor macrophage infiltration and inhibition of angiogenesis.