A Targeted Quantitative Proteomic Method Revealed a Substantial Reprogramming of Kinome during Melanoma Metastasis.

Publication date: Feb 12, 2020

Kinases are involved in numerous critical cell signaling processes, and dysregulation in kinase signaling is implicated in many types of human cancers. In this study, we applied a parallel-reaction monitoring (PRM)-based targeted proteomic method to assess kinome reprogramming during melanoma metastasis in three pairs of matched primary/metastatic human melanoma cell lines. Around 300 kinases were detected in each pair of cell lines, and the results showed that Janus kinase 3 (JAK3) was with reduced expression in the metastatic lines of all three pairs of melanoma cells. Interrogation of The Cancer Genome Atlas (TCGA) data showed that reduced expression of JAK3 is correlated with poorer prognosis in melanoma patients. Additionally, metastatic human melanoma cells/tissues exhibited diminished levels of JAK3 mRNA relative to primary melanoma cells/tissues. Moreover, JAK3 suppresses the migration and invasion of cultured melanoma cells by modulating the activities of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). In summary, our targeted kinome profiling method provided by far the most comprehensive dataset for kinome reprogramming associated with melanoma progression, which builds a solid foundation for examining the functions of other kinases in melanoma metastasis. Moreover, our results reveal a role of JAK3 as a potential suppressor for melanoma metastasis.

Open Access PDF

Miao, W., Li, L., Liu, X., Qi, T.F., Guo, L., Huang, M., and Wang, Y. A Targeted Quantitative Proteomic Method Revealed a Substantial Reprogramming of Kinome during Melanoma Metastasis. 25796. 2020 Sci Rep (10):1.

Concepts Keywords
JAK3 Cancers
Janus Kinase Poorer prognosis melanoma
Kinase Additionally metastatic melanoma
Matrix Metalloproteinases Primary metastatic melanoma
Melanoma RTT
Metastasis Medicine
Metastatic Cancer pathology
MMP Oncology
MRNA Health
Prognosis Medical specialties
Proteomic Melanoma
Sci Janus kinase 3
Suppressor Metastasis
Invasion

Semantics

Type Source Name
disease MESH Melanoma
pathway KEGG Melanoma
disease MESH Metastasis
disease MESH cancers
drug DRUGBANK Coenzyme M
drug DRUGBANK Dabrafenib
drug DRUGBANK Vemurafenib
disease MESH relapse
drug DRUGBANK ATP
drug DRUGBANK Amino acids
drug DRUGBANK Honey
drug DRUGBANK Methionine
disease MESH noma
drug DRUGBANK Trestolone
drug DRUGBANK Albendazole
pathway KEGG Focal adhesion
pathway KEGG Purine metabolism
drug DRUGBANK L-Tyrosine
disease MESH leukemia
drug DRUGBANK Gelatin
disease MESH **p
drug DRUGBANK Proline
drug DRUGBANK Naproxen
drug DRUGBANK L-Lysine
drug DRUGBANK L-Arginine
drug DRUGBANK Tamsulosin

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