The MRPS18-2 protein levels correlate with prostate tumor progression and it induces CXCR4-dependent migration of cancer cells

Abstract

We have earlier found abnormal expression of the mitochondrial ribosomal protein S18-2 (MRPS18-2, S18-2) in endometrial cancer, compared to the expression in hyperplasia and in normal endometrium. Here we report that expression of S18-2 was increased with disease progression in clinical specimens of prostate cancer (PCa). The level of induction of epithelial to mesenchymal cell transition (EMT) correlated with the expression level of S18-2 in PCa cell lines. Moreover, cells acquired increased ability of migration upon S18-2 overexpression, as was evaluated in zebrafish embryo model and in trans-well assay. We found that this is due to increased CXCR4 cell surface expression. Neutralizing CXCR4 protein or abrogating S18-2 expression in cells significantly reduced their migratory ability directed toward CXCL12. The mRNA expression of TWIST2, encoding one of transcription factors that induce EMT upon CXCR4 increase, positively correlated with the S18-2 protein level. Together, these data suggest that the S18-2 protein induces EMT through the TWIST2/E-cadherin signalling and, consequently, CXCR4-mediated migration of PCa cells.

Cell stemness is maintained upon concurrent expression of RB and the mitochondrial ribosomal protein S18-2

“…We next precipitated human KLF4 from PC3 and PC3-S18-2 cells, a PC3 subline that constitutively expresses high levels of S18-2 ( Fig. 5 B ) ( 20 ). Mouse Klf4 was also precipitated to the S 18–2 promoter region from RH18RB cell lysates ( Fig.…”

Human Mitoribosome Biogenesis and Its Emerging Links to Disease

“…mS18b (MRPS18-2) —mS18b protein levels were found to be elevated in prostate cancer tissue; however, additional mechanistic characterization is required to establish a link between mS18b and cancer [ 131 ].…”

Abnormal Expression of Mitochondrial Ribosomal Proteins and Their Encoding Genes with Cell Apoptosis and Diseases

“…Overexpression of MRPS18-B (MRPS18-2) leads to the epithelial cells that acquire a higher migration ability to transform as mesenchymal cell (EMT). Further studies have shown that MRPS18-2 induces EMT through the TWIST2/E-cadherin signal and CXCR4 (PC3 cells express the chemokine receptor) mediates the migration of prostate cancer cells [ 67 ]. Lately, MRPS7 was detected as a key gene in the pathophysiological process of osteosarcoma and the MRPL3 content is positively correlated with the prognosis of osteosarcoma [ 6 ].…”