Evidence map›Paper›PMID 31894856›Full record

ArticleBioscience reports2020

ERRα activates SHMT2 transcription to enhance the resistance of breast cancer to lapatinib via modulating the mitochondrial metabolic adaption.

Xin Li, Kejing Zhang, Yu Hu, Na Luo

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioscience reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.4field-weighted citation impact, top 20% 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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

24 citing papers in PubMed, 28 citations in OpenAlex.

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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

4 authors at 1 institution in 1 country.

Xin LiDepartment of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Kejing ZhangDepartment of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Yu HuDepartment of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Na LuoDepartment of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Central South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Lapatinib, a tyrosine kinase inhibitor, can initially benefit the patients with breast tumors but fails in later treatment due to the inevitable development of drug resistance. Estrogen-related receptor α (ERRα) modulates the metabolic adaptations in lapatinib-resistant cancer cells; however, the underlying mechanism remains unclear. ERRα was predicted to bind to the serine hydroxymethyltransferase 2 (SHMT2) transcription initiation site in the ER- and HER2-positive cell line BT-474; thus, we hypothesize that ERRα might modulate the resistance of breast cancer to lapatinib via regulating SHMT2. In the present study, we revealed that 2.5 and 5 µM lapatinib treatment could significantly decrease the expression and protein levels of ERRα and SHMT2; ERRα and SHMT2 expression and protein levels were significantly up-regulated in breast cancer cells, in particularly in breast cancer cells with resistance to lapatinib. ERRα knockdown restored the inhibitory effects of lapatinib on the BT-474R cell viability and migration; in the meantime, ERRα knockdown rescued the production of reactive oxygen species (ROS) whereas decreased the ratio of glutathione (GSH)/oxidized glutathione (GSSG) upon lapatinib treatment. Via targeting SHMT2 promoter region, ERRα activated the transcription of SHMT2. The effects of ERRα knockdown on BT-474R cells under lapatinib treatment could be significantly reversed by SHMT2 overexpression. In conclusion, ERRα knockdown suppresses the detoxification and the mitochondrial metabolic adaption in breast cancer resistant to lapatinib; ERRα activates SHMT2 transcription via targeting its promoter region, therefore enhancing breast cancer resistance to lapatinib.

Indexed as

Drug Resistance, NeoplasmAntineoplastic AgentsBinding SitesBreast NeoplasmsCell Line, TumorEnergy MetabolismERRalpha Estrogen-Related ReceptorFemaleGene Expression Regulation, NeoplasticGlycine HydroxymethyltransferaseHumansLapatinibMitochondriaPromoter Regions, GeneticProtein Kinase InhibitorsReactive Oxygen SpeciesAntineoplastic AgentsERRalpha Estrogen-Related ReceptorGlycine HydroxymethyltransferaseLapatinibProtein Kinase InhibitorsReactive Oxygen SpeciesReceptors, EstrogenSHMT protein, humanbreast cancerERRαlapatinibmitochondrial metabolic adaptionresistanceSHMT2

Identifiers

PMID31894856
PMCPMC6970080
OpenAlexW2997654221

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Read underepoch 390

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 OpenQuestion graph.