The Genome-Wide Analysis of Carcinoembryonic Antigen Signaling by Colorectal Cancer Cells Using RNA Sequencing
Abstract
Сarcinoembryonic antigen (CEA, CEACAM5, CD66) is a promoter of metastasis in epithelial cancers that is widely used as a prognostic clinical marker of metastasis. The aim of this study is to identify the network of genes that are associated with CEA-induced colorectal cancer liver metastasis. We compared the genome-wide transcriptomic profiles of CEA positive (MIP101 clone 8) and CEA negative (MIP 101) colorectal cancer cell lines with different metastatic potential in vivo. The CEA-producing cells displayed quantitative changes in the level of expression for 100 genes (over-expressed or down-regulated). They were confirmed by quantitative RT-PCR. The KEGG pathway analysis identified 4 significantly enriched pathways: cytokine-cytokine receptor interaction, MAPK signaling pathway, TGF-beta signaling pathway and pyrimidine metabolism. Our results suggest that CEA production by colorectal cancer cells triggers colorectal cancer progression by inducing the epithelial- mesenchymal transition, increasing tumor cell invasiveness into the surrounding tissues and suppressing stress and apoptotic signaling. The novel gene expression distinctions establish the relationships between the existing cancer markers and implicate new potential biomarkers for colorectal cancer hepatic metastasis.
Additional Information
© 2016 Bajenova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received: April 12, 2016; Accepted: August 2, 2016; Published: September 1, 2016. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. This work was financially supported by the Russian Foundation for Fundamental Research, grant RFFI # 11-04-01711 to OB, by the Government of the Russian Federation mega grant 11G34.31.0068 to SO. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist. We thank Dr. Peter Thomas (Creighton University, Omaha, USA) for providing the MIP101 cell lines. We also thank Dr. S. Simonov (Theodosius Dobzhansky Center for Genome Bioinformatics at St. Petersburg State University) for useful advice in the data analysis and E. Tkach (University of Massachusetts at Amherst) for the careful proof reading of our manuscript and valuable suggestions. Author Contributions: Conceived and designed the experiments: OB SJO. Performed the experiments: OB AS SG IE AG EB. Analyzed the data: OB IE MR AS AG. Contributed reagents/materials/analysis tools: OB SJO AS EB SG AG. Wrote the paper: OB SJO IE AG MR EB.Attached Files
Published - journal.pone.0161256.PDF
Supplemental Material - journal.pone.0161256.s001.DOCX
Supplemental Material - journal.pone.0161256.s002.DOCX
Supplemental Material - journal.pone.0161256.s003.DOCX
Supplemental Material - journal.pone.0161256.s004.DOCX
Files
Name | Size | Download all |
---|---|---|
md5:77f8a4e1e35c3640131f73316f9d72ea
|
16.8 kB | Download |
md5:dd5c8272462b9ea99151fb3c01bf3196
|
537.8 kB | Download |
md5:def1c0b312714a0b1bc947eaa6b1980a
|
19.5 kB | Download |
md5:fe44fd8eadca4b2896f602d2583218c4
|
1.3 MB | Preview Download |
md5:3305d6eb4a217be4a1d7f7575dfaf243
|
24.1 kB | Download |
Additional details
- PMCID
- PMC5008809
- Eprint ID
- 70297
- Resolver ID
- CaltechAUTHORS:20160913-090623240
- 11-04-01711
- Russian Foundation for Fundamental Research
- 11G34.31.0068
- Russian Federation
- Created
-
2016-09-13Created from EPrint's datestamp field
- Updated
-
2023-03-16Created from EPrint's last_modified field