Evidence map›Paper›PMID 29720121›Full record

ArticleBMC cancer2018

C-Cbl reverses HER2-mediated tamoxifen resistance in human breast cancer cells.

Wei Li, Ling Xu, Xiaofang Che, Haizhou Li, Ye Zhang, Na Song, Ti Wen, Kezuo Hou, Yi Yang, Lu Zhou and 7 more

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

Article in BMC cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
0.4field-weighted citation impact, top 35% 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

11 citing papers in PubMed, 17 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

17 authors at 3 institutions in 1 country.

Wei LiDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Ling XuDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Xiaofang CheDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Haizhou LiJinzhou Center Hospital, Jinzhou, 121000, Liaoning, China.
Ye ZhangDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Na SongDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Ti WenDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Kezuo HouDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Yi YangLaboratory Animal Center, China Medical University, Shenyang, 110001, Liaoning, China.
Lu ZhouDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Xing XinDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Lu XuDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Xue ZengDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Sha ShiDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Yunpeng LiuDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Xiujuan QuDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China. xiujuanqu@yahoo.com.
Yuee TengDepartment of Medical Oncology, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China. yeteng@cmu.edu.cn.ORCID http://orcid.org/0000-0002-9198-9795
First Hospital of China Medical University · CNChina Medical University · CNJinzhou Central Hospital · CN

Funding

Department of Education of Liaoning Province L2015588Jinzhou Science and Technology Project 17B1E37National Natural Science Foundation of China 31770963National Natural Science Foundation of China 81172535National Natural Science Foundation of China 81672605National Natural Science Foundation of China 81673025Natural Science Foundation of Liaoning Province 2015020458
6 · The paper itself

Abstract

backgroundTamoxifen is a frontline therapy for estrogen receptor (ER)-positive breast cancer in premenopausal women. However, many patients develop resistance to tamoxifen, and the mechanism underlying tamoxifen resistance is not well understood. Here we examined whether ER-c-Src-HER2 complex formation is involved in tamoxifen resistance.

methodsMTT and colony formation assays were used to measure cell viability and proliferation. Western blot was used to detect protein expression and protein complex formations were detected by immunoprecipitation and immunofluorescence. SiRNA was used to examine the function of HER2 in of BT474 cells. An in vivo xenograft animal model was established to examine the role of c-Cbl in tumor growth.

resultsMTT and colony formation assay showed that BT474 cells are resistant to tamoxifen and T47D cells are sensitive to tamoxifen. Immunoprecipitation experiments revealed ER-c-Src-HER2 complex formation in BT474 cells but not in T47D cells. However, ER-c-Src-HER2 complex formation was detected after overexpressing HER2 in T47D cells and these cells were more resistant to tamoxifen. HER2 knockdown by siRNA in BT474 cells reduced ER-c-Src-HER2 complex formation and reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was also disrupted and tamoxifen resistance was reversed in BT474 cells by the c-Src inhibitor PP2 and HER2 antibody trastuzumab. Nystatin, a lipid raft inhibitor, reduced ER-c-Src-HER2 complex formation and partially reversed tamoxifen resistance. ER-c-Src-HER2 complex formation was disrupted by overexpression of c-Cbl but not by the c-Cbl ubiquitin ligase mutant. In addition, c-Cbl could reverse tamoxifen resistance in BT474 cells, but the ubiquitin ligase mutant had no effect. The effect of c-Cbl was validated in BT474 tumor-bearing nude mice in vivo. Immunofluorescence also revealed ER-c-Src-HER2 complex formation was reduced in tumor tissues of nude mice with c-Cbl overexpression.

conclusionsOur results suggested that c-Cbl can reverse tamoxifen resistance in HER2-overexpressing breast cancer cells by inhibiting the formation of the ER-c-Src-HER2 complex.

Indexed as

AnimalsBreast NeoplasmsCell Line, TumorCSK Tyrosine-Protein KinaseDrug Resistance, NeoplasmErb-b2 Receptor Tyrosine KinasesFemaleHeterograftsHumansMiceMice, NudeProto-Oncogene Proteins c-cblReceptors, EstrogenSelective Estrogen Receptor Modulatorssrc-Family KinasesTamoxifenCBL protein, humanCSK protein, humanCSK Tyrosine-Protein KinaseERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesProto-Oncogene Proteins c-cblReceptors, EstrogenSelective Estrogen Receptor Modulatorssrc-Family KinasesTamoxifenBreast cancerC-CblHER2ResistanceTamoxifen

Identifiers

PMID29720121
PMCPMC5930956
OpenAlexW2807467153

What OpenQuestion 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 OpenQuestion graph.