Cited by 23Folate and B Vitamins ResearchColorectal Cancer Treatments and StudiesEpigenetics and DNA Methylation

Association of transcriptional levels of folate-mediated one-carbon metabolism-related genes in cancer cell lines with drug treatment response

Min, Dong-Joon, Vural, Suleyman, Krushkal, Julia·2019·Cancer Genetics

Abstract

Folate-mediated one-carbon metabolism is essential for growth and survival of cancer cells. We investigated whether the response of cancer cells to antitumor treatment may be partially influenced by variation in expression of one-carbon metabolism genes. We used cancer cell line information from the Cancer Cell Line Encyclopedia and the Genomics of Drug Sensitivity in Cancer resources to examine whether variation in pretreatment expression of one-carbon metabolism-related genes was associated with response to treatment. GART, TYMS, SHMT2, MTR, ALDH2, BHMT, MAT2B, MTHFD2, NNMT, and SLC46A1 showed modest statistically significant correlations with response to a variety of antitumor agents. Higher expression levels of SLC46A1 were associated with resistance to multiple agents, whereas elevated expression of GART, TYMS, SHMT2, MTR, BHMT, and MAT2B was associated with chemosensitivity to multiple drugs. NNMT expression was bimodally distributed and showed different directions of association with various agents. Correlation of increased NNMT expression with sensitivity to dasatinib was validated in the NCI-60 cancer cell line panel. Pretreatment expression levels were correlated among many one-carbon metabolism genes. Expression of several folate genes was strongly associated with expression of multiple components of drug target pathways. Molecular mechanisms underlying associations of one-carbon metabolism gene with drug response require further investigation.

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Crossref · 10.1016/j.cancergen.2019.05.005

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Authors
Min, D.-J., Vural, S., & Krushkal, J.
Affiliations
National Cancer Institute (US)
Corresponding author
Krushkal, Julia
Venue
Cancer Genetics
Publisher
Elsevier BV
Published
2019-09
Volume
237
Pages
19-38
ISSN
2210-7762 (ISSN-L)
OpenAlex
W2951812581
Cited by
23
References
107
Citations by year
2026: 1 · 2022: 5 · 2021: 12 · 2020: 5
FWCI
4.17
Type
journal article
Language
en
Open access
closed
Locations
  • Cancer Genetics (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
cancer cell lines, drug sensitivity, chemosensitivity, drug resistance, gene expression, GART, thymidylate synthase, SHMT2, MTR, ALDH2, BHMT, MAT2B, MTHFD2, nicotinamide N-methyltransferase, SLC46A1, dasatinib, NCI-60, Cancer Cell Line Encyclopedia, GDSC
MeSH terms
Antineoplastic Agents, Carbon, Folic Acid, Humans, Neoplasms, Transcription, Genetic, Gene Expression Profiling, Cell Line, Tumor

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