Inhibition of Met results in concomitant inhibition of Akt and STAT3 signaling pathways, while abrogation of negative feedback permits Erk reactivation

ABSTRACT: Amplification and activation of the Met receptor tyrosine kinase occurs up to 23% of gastric cancers, suggesting that Met is a therapeutic target in these cancers. However, the steady-state signaling events that occur during chronic Met activation, and mechanisms for resistance to Met small-molecule inhibitors, are poorly understood. Here we show that multiple gastric cancer cell lines harboring MET amplifications are dependent on Met signaling for proliferation and anchorage-independent growth. In these cells, short-term inhibition of Met leads to coordinated changes in gene expression; these include a rapid loss in expression of immediate-early genes, followed by decreased expression of genes involved in cell cycle and proliferation. Activation of Ras-Erk, PI3K-Akt and STAT3 pathway

ORGANISM(S): Homo sapiens

SUBMITTER: Sean Cory 

PROVIDER: E-GEOD-54532 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress