6533b871fe1ef96bd12d199b
RESEARCH PRODUCT
Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer.
Guido GambaraMarta BaiocchiGabriella MinchiottiM L De AngelisFederica FrancescangeliKiichi WatanabeMatilde TodaroAlfredo PagliucaR De MariaAnn ZeunerNadia P. CastroAlessandro FiorenzanoDavid S. SalomonPaola ContavalliAlessandra BoeGiorgio StassiCarolina Preziososubject
Colorectal cancerColorectal NeoplasmCriptoMiceIntercellular Signaling Peptides and ProteinTumor Cells CulturedRegulation of gene expressionCulturedstem cell; CRIPTO 1GPI-Linked ProteinCell biologyNeoplasm ProteinsTumor CellsGene Expression Regulation NeoplasticGenes srcNeoplastic Stem CellsIntercellular Signaling Peptides and ProteinsFemaleStem cellColorectal NeoplasmsHumanSignal Transductioncolorectal cancerBiologyGPI-Linked ProteinsAnimals; Colorectal Neoplasms; Female; GPI-Linked Proteins; Gene Expression Regulation Neoplastic; Genes src; Humans; Intercellular Signaling Peptides and Proteins; Mice; Neoplasm Proteins; Neoplastic Stem Cells; Proto-Oncogene Proteins c-akt; Signal Transduction; Spheroids Cellular; Tumor Cells Cultured; Cell Biology; Molecular BiologyNeoplasm ProteinCancer stem cellSettore MED/04 - PATOLOGIA GENERALESpheroids CellularmedicineGene silencingAnimalsHumansClonogenic assayProtein kinase BMolecular BiologysrcOriginal PaperNeoplasticAnimalCell Biologymedicine.diseaseGene Expression RegulationGenesNeoplastic Stem CellCellularSpheroidsanimals; colorectal neoplasms; female; GPI-linked proteins; gene expression regulation; neoplastic; genes src; humans; intercellular signaling peptides and proteins; mice; neoplasm proteins; neoplastic stem cells; proto-oncogene proteins c-akt; signal transduction; spheroids; cellular; tumor cells; culturedAnimals; Colorectal Neoplasms; Female; GPI-Linked Proteins; Gene Expression Regulation Neoplastic; Genes src; Humans; Intercellular Signaling Peptides and Proteins; Mice; Neoplasm Proteins; Neoplastic Stem Cells; Proto-Oncogene Proteins c-akt; Signal Transduction; Spheroids Cellular; Tumor Cells Cultured; Molecular Biology; Cell BiologyProto-Oncogene Proteins c-aktdescription
Stemness was recently depicted as a dynamic condition in normal and tumor cells. We found that the embryonic protein Cripto-1 (CR1) was expressed by normal stem cells at the bottom of colonic crypts and by cancer stem cells (CSCs) in colorectal tumor tissues. CR1-positive populations isolated from patient-derived tumor spheroids exhibited increased clonogenic capacity and expression of stem-cell-related genes. CR1 expression in tumor spheroids was variable over time, being subject to a complex regulation of the intracellular, surface and secreted protein, which was related to changes of the clonogenic capacity at the population level. CR1 silencing induced CSC growth arrest in vitro with a concomitant decrease of Src/Akt signaling, while in vivo it inhibited the growth of CSC-derived tumor xenografts and reduced CSC numbers. Importantly, CR1 silencing in established xenografts through an inducible expression system decreased CSC growth in both primary and metastatic tumors, indicating an essential role of CR1 in the regulation the CSC compartment. These results point to CR1 as a novel and dynamically regulated effector of stem cell functions in colorectal cancer.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2015-01-01 |