Increased immunohistochemical scores for pan-RAS and MEK1 and less nodal metastasis were associated with enhanced survival rates in acral and NCSD melanoma patients.
Furthermore, the promotive effects of ELF3 on cellular proliferation and metastasis could be rescued by Ly294002 (inhibitor of PI3K) and U0126 (inhibitor of MEK1/2).
NRAS mutations were associated with vemurafenib use (p = 0.045) and intracranial metastases (p = 0.036), and MEK1/2 mutations correlated with hepatic progression (p = 0.011).
Microarray analysis demonstrated that HM-3 at high dose could up-regulate the transcription of AKT1 and MEK1, which resulted in the promotion of tumorigenesis and metastasis.
Targeting any member of the signaling cascade reduced metastasis but inhibition of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (Mek) 1 and Mek 2 almost completely prevented lung tumor development.
To investigate the role of HGF/c-met signaling on metastasis in cancer cells stimulated with HGF, we examined the effects of a specific MEK1 inhibitor (PD98059) and a p38 MAP kinase inhibitor (SB203580) on HGF-induced uPA expression in pancreatic cancer cell lines, L3.6PL and IMIM-PC2.