Simultaneous inhibition of the HGF/MET and Erk1/2 pathways affect uveal melanoma cell growth and migration.

ABSTRACT:

Purpose

Nearly all primary uveal melanoma (UM) that metastasize involve the liver. Hepatocyte growth factor (HGF) is proposed to be an important microenvironmental element in attracting/supporting UM metastasis through activation of MET. The majority (>85%) of UM express mutations in the G-alpha proteins, that drive the MEK-ERK1/2 pathway. Thus, we proposed that the combination of MET and MEK inhibition would inhibit the growth and migration of G-alpha protein mutant versus non-mutant UM cells.

Methods

Western-blots demonstrated the relative protein levels of ERK1/2 and MET in UM cells. Cells were treated with the small molecule inhibitors AZD6244 (MEKi) and/or MK-8033 (METi) and downstream markers evaluated. Further studies determined the effect of combination MEKi and METi

SUBMITTER: Chattopadhyay C 

PROVIDER: S-EPMC3923717 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature