Evidence map›Paper›PMID 37378696›Full record

ArticleBreast cancer research and treatment2023

HSD17B4 methylation enhances glucose dependence of BT-474 breast cancer cells and increases lapatinib sensitivity.

Nobuaki Arai, Naoko Hattori, Satoshi Yamashita, Yu-Yu Liu, Takahiro Ebata, Chihiro Takeuchi, Hideyuki Takeshima, Satoshi Fujii, Haruhiko Kondo, Hirofumi Mukai and 1 more

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Article in Breast cancer research and treatment, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 33% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 2 countries.

Nobuaki AraiDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Naoko HattoriDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Satoshi YamashitaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Yu-Yu LiuDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Takahiro EbataDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Chihiro TakeuchiDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Hideyuki TakeshimaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan.
Satoshi FujiiDepartment of Molecular Pathology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
Haruhiko KondoDepartment of Surgery, Kyorin University School of Medicine, Tokyo, Japan.
Hirofumi MukaiDepartment of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
Toshikazu UshijimaDivision of Epigenomics, National Cancer Center Research Institute, Tokyo, Japan. tushijima142@hoshi.ac.jp.ORCID http://orcid.org/0000-0003-3405-7817
Hoshi University · JPKyorin University · JPNational Cancer Center Hospital East · JPYokohama City University · JP

Funding

Japan Agency for Medical Research and Development JP19ck0106466Japan Agency for Medical Research and Development JP23ck0106832
6 · The paper itself

Abstract

purposeHER2-positive breast cancer has a high chance of achieving pathological complete response when HSD17B4, responsible for peroxisomal β-oxidation of very long-chain fatty acids (VLCFA) and estradiol, is methylation-silenced. Here, we aimed to identify the underlying molecular mechanism.

methodsUsing a HER2-positive breast cancer cell line, BT-474, control and knock-out (KO) clones were obtained. Metabolic characteristics were analyzed using a Seahorse Flux analyzer.

resultsHSD17B4 KO suppressed cellular proliferation, and enhanced sensitivity to lapatinib approximately tenfold. The KO led to accumulation of VLCFA and a decrease of polyunsaturated fatty acids (PUFAs), such as docosahexaenoic acid (DHA) and arachidonic acid. HSD17B4 KO increased Akt phosphorylation, possibly via decreased DHA, and genes involved in oxidative phosphorylation (OxPhos) and electron transport chain (ETC) were upregulated. Increased mitochondrial ATP production in the KO cells was confirmed by extracellular flux analyzer. Increased OxPhos led to severe dependence of the KO cells on pyruvate from glycolysis. Suppression of glycolysis by lapatinib led to severe delayed suppression of OxPhos in KO cells.

conclusionHSD17B4 KO in BT-474 cells caused a decrease of PUFAs, increased Akt phosphorylation, enhanced glucose dependence of OxPhos, and increased sensitivity to inhibition of HER2, upstream of Akt. This mechanism may be applicable to other HER2-positive glucose-dependent breast cancer cells with HSD17B4 silencing.

Indexed as

Breast NeoplasmsCell Line, TumorErb-b2 Receptor Tyrosine KinasesFemaleGlucoseHumansLapatinibMethylationPeroxisomal Multifunctional Protein-2Proto-Oncogene Proteins c-aktErb-b2 Receptor Tyrosine KinasesGlucoseHSD17B4 protein, humanLapatinibPeroxisomal Multifunctional Protein-2Proto-Oncogene Proteins c-aktDNA methylationEpigeneticsHER2-positive breast cancerMetabolic vulnerabilityNeoadjuvant chemotherapy

Identifiers

PMID37378696
OpenAlexW4382345044

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.