Shen et al., "Metastasis suppressor gene Raf kinase inhibitor protein (RKIP) is a novel prognostic marker in prostate cancer," Prostate, vol.
Oueslati, "A comparison of the biological features of prostate cancer with (PSA+, PSMA+) profile according to RKIP," BioMed Research International, vol.
Rosner, "RKIP suppresses breast cancer metastasis to the bone by regulating stroma-associated genes," International Journal of Breast Cancer, vol.
Bonavida, "Raf Kinase Inhibitor Protein (RKIP) blocks signal transducer and activator of transcription 3 (STAT3) activation in breast and prostate cancer," PLoS One, vol.
Wang et al., "RKIP sensitizes prostate and breast cancer cells to drug-induced apoptosis," The Journal of Biological Chemistry, vol.
Abbreviations: FOXC1, forkhead box C1; H3K27me3, H3K27 trimethylation; miRNAs, microRNAs; PAX8, paired box gene 8; PRC2, polycomb repressive complex 2; PSP94, prostate secretory protein of 94 amino acids; Rap1, Ras-proximate-1 or Ras-related protein 1; Rap1GAP, Rap1 GTPase-activating protein; RKIP
, Raf-1 kinase inhibitor protein; RUNX3, Runt-related transcription factor 3 gene.
"Prior research suggests that RKIP plays a seminal role in inhibiting cancer metastasis, but, until now, the mechanisms underlying this activity were not clear," said Fisher.
Through their experiments, the scientists discovered that RKIP physically binds with mda-9/syntenin, and this physical interaction inhibits mda-9/syntenin expression.
Additionally, the team found that levels of mda-9/syntenin were higher than levels of RKIP in malignant and metastatic melanoma cells while levels of RKIP were higher than levels of mda-9/syntenin in healthy melanocytes, which are the cells that produce pigment in the skin, eyes and hair.
Now that the researchers have demonstrated the ability of RKIP to inhibit mda-9/syntenin-mediated metastasis, they are focusing their attention on developing small molecules imitating RKIP that could be used as new treatments for melanoma.
protein, which is produced naturally in the body, acts like a brake to help slow the spread of the disease.
Loss of RKIP
expression is associated with poor survival in GISTs.