KnockdownofRonKinaseInhibitsMutantPhosphatidylinositol 3-KinaseandReducesMetastasisinHumanColonCarcinoma *

Abnormal accumulation and activation of receptor tyro-sine kinase Ron (recepteur d’origine nantais) has been dem-onstrated in a variety of primary human cancers. We showthatRNAinterference-mediatedknockdownofRonkinaseina highly tumorigenic colon cancer cell line led to reducedproliferationascomparedwiththecontrolcells.DecreasedRonexpression sensitized HCT116 cells to growth factor depriva-tion stress-induced apoptosis as reflected by increased DNAfragmentationandcaspase3activation.Inaddition,cellmotilitywas decreased in Ron knockdown cells as measured by woundhealingassaysandtranswellassays.HCT116cellsareheterozy-gous for gain of function mutant