Ran GTPase promotes cancer progression via Met receptor-mediated downstream signaling

摘要: It has been shown previously that cancer cells with an activated oncogenic pathway, including Met activation, require Ran for growth and survival.Here, we show knockdown of leads to a reduction receptor expression in several breast lung cell lines. This, turn suppressed HGF the Met-mediated activation Akt as well adhesion, migration, invasion. In line model where amplification contribute gefitinib resistance, sensitized gefitinib-mediated inhibition ERK1/2 phosphorylation consequently reduced proliferation. We further demonstrate reduction-mediated by Ran, occurs at post-transcriptional level, probably via matrix metalloproteinase. Moreover, level immunoreactive are positively associated human specimens, suggesting high may be pre-requisite overexpression. Interestingly, dictates prognostic significance Met, indicating co-overexpression progression could used combination indicator.