Evidence map›Paper›PMID 30050079›Full record

ArticleCell death & disease2018

Co-inhibition of mTORC1, HDAC and ESR1α retards the growth of triple-negative breast cancer and suppresses cancer stem cells.

Andrew Sulaiman, Sarah McGarry, Ka Mien Lam, Sara El-Sahli, Jason Chambers, Shelby Kaczmarek, Li Li, Christina Addison, Jim Dimitroulakos, Angel Arnaout and 9 more

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

Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

30 citing papers in PubMed, 45 citations in OpenAlex.

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  11. Ribosomal Protein S6: A Potential Therapeutic Target against Cancer?International journal of molecular sciences · 2021
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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

19 authors at 6 institutions in 2 countries.

Andrew SulaimanDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Sarah McGarryDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Ka Mien LamDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Sara El-SahliDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Jason ChambersDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Shelby KaczmarekDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Li LiDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Christina AddisonDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Jim DimitroulakosDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Angel ArnaoutCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
Carolyn NessimCentre for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, ON, K1H 8L6, Canada.
Zemin YaoDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Guang JiChina-Canada Centre of Research for Digestive Diseases, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Haiyan SongChina-Canada Centre of Research for Digestive Diseases, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Sheng LiuInstitute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, 200032, Shanghai, China.
Ying XieInstitute of Chinese Traditional Surgery, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, 200032, Shanghai, China.
Suresh GaddeDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Xuguang LiDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
Lisheng WangDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. Lisheng.Wang@uottawa.ca.
University of Ottawa · CAOttawa Hospital · CALonghua Hospital Shanghai University of Traditional Chinese Medicine · CNShanghai University of Traditional Chinese Medicine · CNHealth Canada · CAOttawa Hospital Research Institute

Funding

CIHR MOP-111224
6 · The paper itself

Abstract

Triple-negative breast cancer (TNBC) is the most refractory subtype of breast cancer. It causes the majority of breast cancer-related deaths, which has been largely associated with the plasticity of tumor cells and persistence of cancer stem cells (CSCs). Conventional chemotherapeutics enrich CSCs and lead to drug resistance and disease relapse. Development of a strategy capable of inhibiting both bulk and CSC populations is an unmet medical need. Inhibitors against estrogen receptor 1, HDACs, or mTOR have been studied in the treatment of TNBC; however, the results are inconsistent. In this work, we found that patient TNBC samples expressed high levels of mTORC1 and HDAC genes in comparison to luminal breast cancer samples. Furthermore, co-inhibition of mTORC1 and HDAC with rapamycin and valproic acid, but neither alone, reproducibly promoted ESR1 expression in TNBC cells. In combination with tamoxifen (inhibiting ESR1), both S6RP phosphorylation and rapamycin-induced 4E-BP1 upregulation in TNBC bulk cells was inhibited. We further showed that fractionated CSCs expressed higher levels of mTORC1 and HDAC than non-CSCs. As a result, co-inhibition of mTORC1, HDAC, and ESR1 was capable of reducing both bulk and CSC subpopulations as well as the conversion of fractionated non-CSC to CSCs in TNBC cells. These observations were partially recapitulated with the cultured tumor fragments from TNBC patients. Furthermore, co-administration of rapamycin, valproic acid, and tamoxifen retarded tumor growth and reduced CD44

Indexed as

Adaptor Proteins, Signal TransducingAnimalsCell Cycle ProteinsCell Line, TumorCell ProliferationEstrogen Receptor alphaFemaleHistone DeacetylasesHumansMechanistic Target of Rapamycin Complex 1MiceMice, NudeNeoplastic Stem CellsPhosphoproteinsRibosomal Protein S6 KinasesRNA InterferenceAdaptor Proteins, Signal TransducingCell Cycle ProteinsEIF4EBP1 protein, humanEstrogen Receptor alphaHistone DeacetylasesMechanistic Target of Rapamycin Complex 1PhosphoproteinsRibosomal Protein S6 KinasesRNA, Small InterferingSirolimusTamoxifenValproic Acid

Identifiers

PMID30050079
PMCPMC6062597
OpenAlexW2883892389

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.