6533b7dbfe1ef96bd1270249
RESEARCH PRODUCT
CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.
Francesco DieliVeronica CatalanoGianfranco CocorulloRuggero De MariaSilvia VolpeGiorgio StassiFlora IovinoMauro BiffoniGaspare GulottaMatilde TodaroTiziana ApuzzoMiriam GaggianesiAntonina BenfanteIsabella Sperdutisubject
CA15-3Animals; Biomarkers Tumor; Bone Morphogenetic Proteins; Carcinogenesis; Colonic Neoplasms; Fibroblasts; Humans; Hyaluronan Receptors; Mice SCID; Neoplasm Metastasis; Neoplasm Proteins; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Signal Transduction; Treatment Outcome; Wnt Proteins; Cellular Reprogramming; Molecular Medicine; Genetics; Cell BiologyCarcinogenesisWnt ProteinMice SCIDmedicine.disease_causeAnimals; Antigens CD44; Biomarkers Tumor; Bone Morphogenetic Proteins; Carcinogenesis; Colonic Neoplasms; Fibroblasts; Humans; Mice SCID; Neoplasm Metastasis; Neoplasm Proteins; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Signal Transduction; Treatment Outcome; Wnt Proteins; Cellular ReprogrammingMetastasisMicePhosphatidylinositol 3-KinasesCD44Neoplasm MetastasisCarcinogenesiPhosphoinositide-3 Kinase InhibitorsColonic NeoplasmTumorbiologyProto-Oncogene Proteins c-metCellular ReprogrammingPrognosisAntigens CD44Neoplasm ProteinsNeoplasm MetastasiAnimals; Antigens CD44; Biomarkers Tumor; Bone Morphogenetic Proteins; Carcinogenesis; Colonic Neoplasms; Fibroblasts; Humans; Mice SCID; Neoplasm Metastasis; Neoplasm Proteins; Neoplastic Stem Cells; Phosphatidylinositol 3-Kinases; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-met; Signal Transduction; Treatment Outcome; Wnt Proteins; Cellular Reprogramming; Cell Biology; Molecular Medicine; GeneticsHyaluronan ReceptorsTreatment OutcomeBone Morphogenetic ProteinsColonic NeoplasmsNeoplastic Stem CellsFibroblastMolecular MedicineHepatocyte growth factorStem cellHumanmedicine.drugSignal TransductionPrognosiProtein Kinase InhibitorSCIDNeoplasm ProteinCancer stem cellSettore MED/04 - PATOLOGIA GENERALEmedicineGeneticsBiomarkers TumorAnimalsHumansAntigensProgenitor cellProtein Kinase InhibitorsSettore MED/04 - Patologia GeneraleAnimalBone Morphogenetic Proteincancer metastasisCD44Cell BiologyFibroblastsmedicine.diseaseWnt ProteinsSettore MED/18 - Chirurgia GeneraleImmunologyCancer researchbiology.proteinNeoplastic Stem CellPhosphatidylinositol 3-KinaseCarcinogenesisBiomarkersdescription
SummaryCancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6− progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-03-01 | Cell stem cell |