Evidence map›Paper›PMID 36918912›Full record

ArticleBreast cancer research : BCR2023

MUC16 promotes triple-negative breast cancer lung metastasis by modulating RNA-binding protein ELAVL1/HUR.

Sanjib Chaudhary, Muthamil Iniyan Appadurai, Shailendra Kumar Maurya, Palanisamy Nallasamy, Saravanakumar Marimuthu, Ashu Shah, Pranita Atri, Chirravuri Venkata Ramakanth, Subodh M Lele, Parthasarathy Seshacharyulu and 5 more

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In one paragraph

Article in Breast cancer research : BCR, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
6.8field-weighted citation impact, top 3% 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

17 citing papers in PubMed, 44 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

15 authors at 2 institutions in 1 country.

Sanjib ChaudharyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Muthamil Iniyan AppaduraiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Shailendra Kumar MauryaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Palanisamy NallasamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Saravanakumar MarimuthuDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Ashu ShahDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Pranita AtriDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Chirravuri Venkata RamakanthDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Subodh M LeleDepartment of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, 68198-5900, USA.
Parthasarathy SeshacharyuluDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Mohd W NasserDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Apar Kishor GantiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA. sbatra@unmc.edu.
Imayavaramban LakshmananDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198-5870, USA. ilakshmanan@unmc.edu.
University of Nebraska Medical Center · USVA Nebraska Western Iowa Health Care System · US

Funding

Project 3: MUC16-Mediated Metabolic Reprograming Induces PC MetastasisP01CA217798 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI THAYER, SARAH P · 2018 to 2022
$8.1M
Role of PD2/Paf1 in Pancreatic Acinar to Ductal MetaplasiaR01CA210637 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., PONNUSAMY, MOORTHY P. · 2017 to 2021
$2.0M
Molecular Markers for the Diagnosis of Pancreatic CancerR01CA131944 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2008 to 2012
$1.5M
ST6GalNAc-I/MUC5AC promoting angiogenesis in lung adenocarcinomaR21CA267582 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI LAKSHMANAN, IMAYAVARAMBAN · 2022 to 2023
$387k
BLRD VA I01 BX004676NCI NIH HHS P01 CA217798NCI NIH HHS R01 CA131944NCI NIH HHS R01 CA210637NCI NIH HHS R21 CA267582
6 · The paper itself

Abstract

backgroundTriple-negative breast cancer (TNBC) is highly aggressive with an increased metastatic incidence compared to other breast cancer subtypes. However, due to the absence of clinically reliable biomarkers and targeted therapy in TNBC, outcomes are suboptimal. Hence, there is an urgent need to understand biological mechanisms that lead to identifying novel therapeutic targets for managing metastatic TNBC.

methodsThe clinical significance of MUC16 and ELAVL1 or Hu antigen R (HuR) was examined using breast cancer TCGA data. Microarray was performed on MUC16 knockdown and scramble TNBC cells and MUC16-associated genes were identified using RNA immunoprecipitation and metastatic cDNA array. Metastatic properties of MUC16 were evaluated using tail vein experiment. MUC16 and HuR downstream pathways were confirmed by ectopic overexpression of MUC16-carboxyl-terminal (MUC16-Cter), HuR and cMyc as well as HuR inhibitors (MS-444 and CMLD-2) in TNBC cells.

resultsMUC16 was highly expressed in TNBC and correlated with its target HuR. Depletion of MUC16 showed decreased invasion, migration, and colony formation abilities of human and mouse TNBC cells. Mice injected with MUC16 depleted cells were less likely to develop lung metastasis (P = 0.001). Notably, MUC16 and HuR were highly expressed in the lung tropic TNBC cells and lung metastases. Mechanistically, we identified cMyc as a HuR target in TNBC using RNA immunoprecipitation and metastatic cDNA array. Furthermore, MUC16 knockdown and pharmacological inhibition of HuR (MS-444 and CMLD-2) in TNBC cells showed a reduction in cMyc expression. MUC16-Cter or HuR overexpression models indicated MUC16/HuR/cMyc axis in TNBC cell migration.

conclusionsOur study identified MUC16 as a TNBC lung metastasis promoter that acts through HuR/cMyc axis. This study will form the basis of future studies to evaluate the targeting of both MUC16 and HuR in TNBC patients.

Indexed as

Lung NeoplasmsTriple Negative Breast NeoplasmsAnimalsCA-125 AntigenCell Line, TumorCell MovementCell ProliferationELAV-Like Protein 1FuransGene Expression Regulation, NeoplasticHumansMembrane ProteinsMiceNaphtholsRNA5,8-dihydroxy-3-methyl-4-(9H)-naphtho(2,3-c)furanoneCA-125 AntigenELAVL1 protein, humanELAV-Like Protein 1FuransMembrane ProteinsMUC16 protein, humanNaphtholsRNAcMycELAVL1/HuRMetastasisMMP1MMP3TNBCUC16YB1YBX-1

Identifiers

PMID36918912
PMCPMC10012760
OpenAlexW4324142398

What Socratic holds

Textfull text, public
LicenceCC BY
measurements read47
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 Socratic graph.