In vivo epigenetic reprogramming of primary human colon cancer cells enhances metastases

Autor: Ariel Ruiz i Altaba, Grigori Singovski, Irene Siegl-Cachedenier, Arwen Conod, Carolina Bernal, Monika Kuciak
Jazyk: angličtina
Rok vydání: 2021
Předmět:
cancer stem cells
0301 basic medicine
Enhances metastases
Bioinformatics
Epigenesis
Genetic
ddc:576.5
Neoplasm Metastasis
Epigenetic
Articles
General Medicine
Cellular Reprogramming
Primary tumor
Colon cancer
Gene Expression Regulation
Neoplastic
Phenotype
KLF4
Colonic Neoplasms
DNA methylation
embryonic structures
Neoplastic Stem Cells
biological phenomena
cell phenomena
and immunity
Reprogramming
Signal Transduction
Homeobox protein NANOG
Epithelial-Mesenchymal Transition
epigenetic reprogramming
Mice
Nude
Biology
Kruppel-Like Factor 4
03 medical and health sciences
SOX2
Cancer stem cell
Cell Line
Tumor
Spheroids
Cellular
In vivo
Genetics
medicine
Animals
Humans
Neoplasm Invasiveness
Epigenetics
metastases
Molecular Biology
Cell Biology
DNA Methylation
medicine.disease
Xenograft Model Antitumor Assays
Clone Cells
NANOG
030104 developmental biology
Cancer research
GLI
Transcription Factors
Zdroj: Journal of Molecular Cell Biology, Vol. 8, No 2 (2016) pp. 157-173
Journal of Molecular Cell Biology
ISSN: 1674-2788
Popis: How metastases develop is not well understood and no genetic mutations have been reported as specific metastatic drivers. Here we have addressed the idea that epigenetic reprogramming by GLI-regulated pluripotent stemness factors promotes metastases. Using primary human colon cancer cells engrafted in mice, we find that transient expression of OCT4, SOX2, KLF4 +/- cMYC establishes an enhanced pro-metastatic state in the primary tumor that is stable through sequential engraftments and is transmitted through clonogenic cancer stem cells. Metastatic reprogramming alters NANOG methylation and stably boosts NANOG and NANOGP8 expression. Metastases and reprogrammed EMT-like phenotypes require endogenous NANOG, but enhanced NANOG is not sufficient to induce these phenotypes. Finally, reprogrammed tumors enhance GLI2, and we show that GLI2(high) and AXIN2(low), which are markers of the metastatic transition of colon cancers, are prognostic of poor disease outcome in patients. We propose that metastases arise through epigenetic reprogramming of cancer stem cells within primary tumors.
Databáze: OpenAIRE
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