Unknown

Dataset Information

0

Raf kinase inhibitor RKIP inhibits MDA-9/syntenin-mediated metastasis in melanoma.


ABSTRACT: Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, functions as a positive regulator of melanoma progression and metastasis. In contrast, the Raf kinase inhibitor, RKIP, a negative modulator of RAF-stimulated MEKK activation, is strongly downregulated in metastatic melanoma cells. In this study, we explored a hypothesized inverse relationship between MDA-9 and RKIP in melanoma. Tumor array and cell line analyses confirmed an inverse relationship between expression of MDA-9 and RKIP during melanoma progression. We found that MDA-9 transcriptionally downregulated RKIP in support of a suggested cross-talk between these two proteins. Furthermore, MDA-9 and RKIP physically interacted in a manner that correlated with a suppression of FAK and c-Src phosphorylation, crucial steps necessary for MDA-9 to promote FAK/c-Src complex formation and initiate signaling cascades that drive the MDA-9-mediated metastatic phenotype. Finally, ectopic RKIP expression in melanoma cells overrode MDA-9-mediated signaling, inhibiting cell invasion, anchorage-independent growth, and in vivo dissemination of tumor cells. Taken together, these findings establish RKIP as an inhibitor of MDA-9-dependent melanoma metastasis, with potential implications for targeting this process therapeutically.

SUBMITTER: Das SK 

PROVIDER: S-EPMC3939082 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications


Melanoma differentiation associated gene-9 (MDA-9), also known as syntenin, functions as a positive regulator of melanoma progression and metastasis. In contrast, the Raf kinase inhibitor, RKIP, a negative modulator of RAF-stimulated MEKK activation, is strongly downregulated in metastatic melanoma cells. In this study, we explored a hypothesized inverse relationship between MDA-9 and RKIP in melanoma. Tumor array and cell line analyses confirmed an inverse relationship between expression of MDA  ...[more]

Similar Datasets

| S-EPMC5216907 | biostudies-literature
| S-EPMC6562953 | biostudies-literature
| S-EPMC8869954 | biostudies-literature
| S-EPMC3548987 | biostudies-literature
| S-EPMC5024755 | biostudies-literature
| S-EPMC7551653 | biostudies-literature
| S-EPMC4246646 | biostudies-literature
| S-EPMC3258266 | biostudies-literature
| S-EPMC3530385 | biostudies-literature
| S-EPMC3151072 | biostudies-literature