1. Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer
- Author
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Guido Gambara, Marta Baiocchi, Gabriella Minchiotti, M L De Angelis, Federica Francescangeli, Kiichi Watanabe, Matilde Todaro, Alfredo Pagliuca, R De Maria, Ann Zeuner, Nadia P. Castro, Alessandro Fiorenzano, David S. Salomon, Paola Contavalli, Alessandra Boe, Giorgio Stassi, Carolina Prezioso, Francescangeli, F., Contavalli, P., De Angelis, M., Baiocchi, M., Gambara, G., Pagliuca, A., Fiorenzano, A., Prezioso, C., Boe, A., Todaro, M., Stassi, G., Castro, N., Watanabe, K., Salomon, D., De Maria, R., Minchiotti, G., and Zeuner, A.
- Subjects
Colorectal cancer ,Colorectal Neoplasm ,Cripto ,Mice ,Intercellular Signaling Peptides and Protein ,Tumor Cells, Cultured ,Regulation of gene expression ,Cultured ,stem cell ,CRIPTO 1 ,GPI-Linked Protein ,Cell biology ,Neoplasm Proteins ,Tumor Cells ,Gene Expression Regulation, Neoplastic ,Genes, src ,Neoplastic Stem Cells ,Intercellular Signaling Peptides and Proteins ,Female ,Stem cell ,Colorectal Neoplasms ,Human ,Signal Transduction ,colorectal cancer ,Biology ,GPI-Linked Proteins ,Animals ,Humans ,Proto-Oncogene Proteins c-akt ,Spheroids, Cellular ,Cell Biology ,Molecular Biology ,Neoplasm Protein ,Cancer stem cell ,Settore MED/04 - PATOLOGIA GENERALE ,medicine ,Gene silencing ,Clonogenic assay ,Protein kinase B ,src ,Original Paper ,Neoplastic ,Animal ,medicine.disease ,Gene Expression Regulation ,Genes ,Neoplastic Stem Cell ,Cellular ,Spheroids ,animals ,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 - Abstract
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.
- Published
- 2015
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