Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer

F. Francescangeli, Federica Francescangeli, P. Contavalli, Paola Contavalli, M. L. De Angelis, Maria Laura De Angelis, M. Baiocchi, G. Gambara, A. Pagliuca, Alfredo Pagliuca, A. Fiorenzano, C. Prezioso, A. Boe, M. Todaro, G. Stassi, N. P. Castro, K. Watanabe, D. S. Salomon, Ruggero De Maria Marchiano, G. MinchiottiA. Zeuner

Risultato della ricerca: Contributo in rivistaArticolo in rivista

36 Citazioni (Scopus)


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 SrcAkt 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.
Lingua originaleEnglish
pagine (da-a)1700-1713
Numero di pagine14
RivistaCell Death and Differentiation
Stato di pubblicazionePubblicato - 2015


  • Animals
  • Cell Biology
  • Colorectal Neoplasms
  • Female
  • GPI-Linked Proteins
  • Gene Expression Regulation, Neoplastic
  • Genes, src
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Mice
  • Molecular Biology
  • Neoplasm Proteins
  • Neoplastic Stem Cells
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Spheroids, Cellular
  • Tumor Cells, Cultured


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