Ras Inhibitors Display an Anti-Metastatic Effect by Downregulation of Lysyl Oxidase through Inhibition of the Ras-PI3K-Akt-HIF-1α Pathway

Metastasis stands as the major obstacle for the survival from cancers. Nonetheless most existing anti-cancer drugs inhibit only cell proliferation, and discovery of agents having both anti-proliferative and anti-metastatic properties would be more beneficial. We previously reported the discovery of small-molecule Ras inhibitors, represented by Kobe0065, that displayed anti-proliferative activity on xenografts of human colorectal cancer (CRC) cell line SW480 carrying the K-rasG12Vgene. Here we show that treatment of cancer cells carrying the activated ras genes with Kobe0065 or an siRNA targeting Ras downregulates the expression of lysyl oxidase (LOX), which has been implicated in metastasis.

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