960

CD44

CDW44|CSPG8|ECMR-III|HCELL|HUTCH-I|IN|LHR|MC56|MDU2|MDU3|MIC4|Pgp1;CD44 molecule (Indian blood group);CD44;CD44 molecule (Indian blood group)

CD44 antigen|GP90 lymphocyte homing/adhesion receptor|Hermes antigen|cell surface glycoprotein CD44|chondroitin sulfate proteoglycan 8|epican|extracellular matrix receptor III|hematopoietic cell E- and L-selectin ligand|heparan sulfate proteoglycan|homing

11p13

protein-coding

After separating from a primary tumor, metastasizing cells enter the circulatory system and interact with host cells before lodging in secondary organs. Previous studies have implicated the surface glycoproteins CD44 and carcinoembryonic antigen (CEA) in adhesion, migration, and invasion, suggesting that they may influence metastatic progression. To elucidate the role of these multifunctional molecules while avoiding the potential drawbacks of ectopic expression or monoclonal antibody treatments, we silenced the expression of CD44 and/or CEA in LS174T colon carcinoma cells and analyzed their ability to metastasize in 2 independent mouse models. Quantitative PCR revealed that CD44 knockdown increased lung and liver metastasis >10-fold, while metastasis was decreased by >50% following CEA knockdown. These findings were corroborated by in vitro experiments assessing the metastatic potential of LS174T cells. Cell migration was decreased as a result of silencing CEA but was enhanced in CD44-knockdown cells. In addition, CD44 silencing promoted homotypic aggregation of LS147T cells, a phenotype that was reversed by additional CEA knockdown. Finally, CD44-knockdown cells exhibited greater mechanical compliance than control cells, a property that correlates with increased metastatic potential. Collectively, these data indicate that CEA, but not CD44, is a viable target for therapeutics aimed at curbing colon carcinoma metastasis.