Dataset Information

Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer.

ABSTRACT: Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-derived cell line CTC-MCC-41 was analyzed and compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells. The association between methylation and the transcriptional profile of CTC-MCC-41 was also evaluated. Differentially methylated CpGs were validated with pyrosequencing and qMSP. Compared to primary and metastatic CRC cells, the methylation profile of CTC-MCC-41 was globally different and characterized by a slight predominance of hypomethylated CpGs mainly distributed in CpG-poor regions. Promoter CpG islands and shore regions of CTC-MCC-41 displayed a unique methylation profile that was associated with the transcriptional program and relevant cancer pathways, mainly Wnt signaling. The epigenetic regulation of relevant genes in CTC-MCC-41 was validated. This study provides new insights into the epigenomic landscape of metastasis-competent CTCs, revealing biological information for metastasis development, as well as new potential biomarkers and therapeutic targets for CRC patients.

SUBMITTER: Bao-Caamano A

PROVIDER: S-EPMC10505142 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer.

Bao-Caamano Aida A Costa-Fraga Nicolás N Cayrefourcq Laure L Jácome María Amalia MA Rodriguez-Casanova Aitor A Muinelo-Romay Laura L López-López Rafael R Alix-Panabières Catherine C Díaz-Lagares Angel A

Scientific reports 20230916 1

Circulating tumor cells (CTCs) and epigenetic alterations are involved in the development of metastasis from solid tumors, such as colorectal cancer (CRC). The aim of this study was to characterize the DNA methylation profile of metastasis-competent CTCs in CRC. The DNA methylome of the human CRC-derived cell line CTC-MCC-41 was analyzed and compared with primary (HT29, Caco2, HCT116, RKO) and metastatic (SW620 and COLO205) CRC cells. The association between methylation and the transcriptional p ...[more]

PMID: 37717096

Similar Datasets

Project description:Metabolic reprogramming is one of the essential features of tumor that may dramatically contribute to metastasis and collapse. The metabolic profiling is investigated on the patient derived tissue and cancer cell line derived mouse metastasis xenograft. As well-recognized “seeds” for remote metastasis of tumor, role of circulating tumor cells (CTCs) in the study of metabolic reprogramming feature of tumor is yet to be elucidated. More specifically, whether there is difference of metabolic features of liver metastasis in colorectal cancer (CRC) derived from either CTCs or cancer cell line is still unknown. In this study, comprehensive untargeted metabolomics was performed using high performance liquid chromatography-mass spectrometry (HPLC-MS) in liver metastasis tissues from CT26 cells and CTCs derived mouse models. We identified 288 differential metabolites associated with the pathways such as one carbon pool by folate, folate biosynthesis and histidine metabolism through bioinformation analysis. Multiple gene expression was upregulated in the CTCs derived liver metastasis, specifically some specific enzymes. These results indicated that the metabolite phenotype and corresponding gene expression in the CTCs derived liver metastasis tissues was different from the parental CT26 cells, displaying a specific up-regulation of mRNAs involved in the above metabolism-related pathways. The metabolic profile of CTCs was characterized on the liver metastatic process in colorectal cancer. The invasion ability and chemo drug tolerance of the CTCs derived tumor and metastasis was found to be overwhelming higher than cell line derived counterpart. Identification of the differential metabolites will lead to a better understanding of the hallmarks of the cancer progression and metastasis, which may suggest potential attractive target for treating metastatic CRC. Graphical abstract Image 1 Circulating tumor cell; Metabolomics; Colorectal cancer; Liver metastasis; Mouse models. Highlights • CTCs exhibit stronger invasion ability through metabolic reprogramming and EMT process.• Liver metastases samples from CTCs derived CRC mouse were detected using HPLC-MS platform.• Results of metabolomic analysis and pathway enrichment analysis both indicated that CTCs changed metabolic pathways during liver metastasis, including one carbon pool by folate, folate biosynthesis, histidine metabolism and other pathways.

Dataset Information

Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer.

Publications

Epigenomic analysis reveals a unique DNA methylation program of metastasis-competent circulating tumor cells in colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets