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Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer
- Source :
- Cell death and differentiation 22 (2015): 1700–1713. doi:10.1038/cdd.2015.19, info:cnr-pdr/source/autori:Francescangeli F, Contavalli P, De Angelis ML, Baiocchi M, Gambara G, Pagliuca A, Fiorenzano A, Prezioso C, Boe A, Todaro M, Stassi G, Castro NP, Watanabe K, Salomon DS, De Maria R, Minchiotti G, Zeuner A./titolo:Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer./doi:10.1038%2Fcdd.2015.19/rivista:Cell death and differentiation/anno:2015/pagina_da:1700/pagina_a:1713/intervallo_pagine:1700–1713/volume:22, Cell Death and Differentiation
- Publication Year :
- 2015
- Publisher :
- Edward Arnold, Oxford , Regno Unito, 2015.
-
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.
- 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
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Cell death and differentiation 22 (2015): 1700–1713. doi:10.1038/cdd.2015.19, info:cnr-pdr/source/autori:Francescangeli F, Contavalli P, De Angelis ML, Baiocchi M, Gambara G, Pagliuca A, Fiorenzano A, Prezioso C, Boe A, Todaro M, Stassi G, Castro NP, Watanabe K, Salomon DS, De Maria R, Minchiotti G, Zeuner A./titolo:Dynamic regulation of the cancer stem cell compartment by Cripto-1 in colorectal cancer./doi:10.1038%2Fcdd.2015.19/rivista:Cell death and differentiation/anno:2015/pagina_da:1700/pagina_a:1713/intervallo_pagine:1700–1713/volume:22, Cell Death and Differentiation
- Accession number :
- edsair.doi.dedup.....1c1a4e8d9f466bafbf4a12e6b586cbb9
- Full Text :
- https://doi.org/10.1038/cdd.2015.19