Cancer stem cells drive tumor formation and metastasis,but how they acquire metastatic traits is notwell understood. Here, we show that all colorectalcancer stem cells (CR-CSCs) express CD44v6, whichis required for their migration and generation of metastatictumors. CD44v6 expression is low in primarytumors but demarcated clonogenic CR-CSC populations.Cytokines hepatocyte growth factor (HGF),osteopontin (OPN), and stromal-derived factor 1a(SDF-1), secreted from tumor associated cells, increaseCD44v6 expression in CR-CSCs by activatingthe Wnt/b-catenin pathway, which promotes migrationand metastasis. CD44v6 progenitor cells donot give rise to metastatic lesions but, when treatedwith cytokines, acquire CD44v6 expression and metastaticcapacity. Importantly, phosphatidylinositol3-kinase (PI3K) inhibition selectively killed CD44v6CR-CSCs and reduced metastatic growth. In patientcohorts, low levels of CD44v6 predict increasedprobability of survival. Thus, the metastatic processin colorectal cancer is initiated by CSCs throughthe expression of CD44v6, which is both a functionalbiomarker and therapeutic target.
|Numero di pagine||15|
|Rivista||Cell Stem Cell|
|Stato di pubblicazione||Published - 2014|