PUBLICATION
RSK1 Activation Promotes Invasion in Nodular Melanoma
- Authors
- Salhi, A., Farhadian, J.A., Giles, K.M., Vega-Saenz de Miera, E., Silva, I.P., Bourque, C., Yeh, K., Chhangawala, S., Wang, J., Ye, F., Zhang, D.Y., Hernando-Monge, E., Houvras, Y., Osman, I.
- ID
- ZDB-PUB-150113-3
- Date
- 2015
- Source
- The American journal of pathology 185(3): 704-16 (Journal)
- Registered Authors
- Bourque, Caitlin, Houvras, Yariv
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement*
- Disease Progression
- Humans
- Melanoma/metabolism*
- Melanoma/pathology
- Neoplasm Invasiveness/pathology*
- Phosphorylation
- Ribosomal Protein S6 Kinases, 90-kDa/metabolism*
- Skin Neoplasms/metabolism*
- Skin Neoplasms/pathology
- Zebrafish
- PubMed
- 25579842 Full text @ Am. J. Pathol.
Citation
Salhi, A., Farhadian, J.A., Giles, K.M., Vega-Saenz de Miera, E., Silva, I.P., Bourque, C., Yeh, K., Chhangawala, S., Wang, J., Ye, F., Zhang, D.Y., Hernando-Monge, E., Houvras, Y., Osman, I. (2015) RSK1 Activation Promotes Invasion in Nodular Melanoma. The American journal of pathology. 185(3):704-16.
Abstract
The two major melanoma histologic subtypes, superficial spreading and nodular melanomas, differ in their speed of dermal invasion but converge biologically once they invade and metastasize. Herein, we tested the hypothesis that distinct molecular alterations arising in primary melanoma cells might persist as these tumors progress to invasion and metastasis. Ribosomal protein S6 kinase, 90 kDa, polypeptide 1 (RSK1; official name RPS6KA1) was significantly hyperactivated in human melanoma lines and metastatic tissues derived from nodular compared with superficial spreading melanoma. RSK1 was constitutively phosphorylated at Ser-380 in nodular but not superficial spreading melanoma and did not directly correlate with BRAF or MEK activation. Nodular melanoma cells were more sensitive to RSK1 inhibition using siRNA and the pharmacological inhibitor BI-D1870 compared with superficial spreading cells. Gene expression microarray analyses revealed that RSK1 orchestrated a program of gene expression that promoted cell motility and invasion. Differential overexpression of the prometastatic matrix metalloproteinase 8 and tissue inhibitor of metalloproteinases 1 in metastatic nodular compared with metastatic superficial spreading melanoma was observed. Finally, using an in vivo zebrafish model, constitutive RSK1 activation increased melanoma invasion. Together, these data reveal a novel role for activated RSK1 in the progression of nodular melanoma and suggest that melanoma originating from different histologic subtypes may be biologically distinct and that these differences are maintained as the tumors invade and metastasize.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping