Evidence map›Paper›PMID 26035354›Full record

ArticleOncotarget2015

Novel HER3/MUC4 oncogenic signaling aggravates the tumorigenic phenotypes of pancreatic cancer cells.

Imayavaramban Lakshmanan, Parthasarathy Seshacharyulu, Dhanya Haridas, Satyanarayana Rachagani, Suprit Gupta, Suhasini Joshi, Chittibabu Guda, Ying Yan, Maneesh Jain, Apar K Ganti and 2 more

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

Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% 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

27 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.

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  11. Presence and structure-activity relationship of intrinsically disordered regions across mucins.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
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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

12 authors at 1 institution in 1 country.

Imayavaramban LakshmananDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Parthasarathy SeshacharyuluDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Dhanya HaridasDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Satyanarayana RachaganiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Suprit GuptaDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Suhasini JoshiDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Chittibabu GudaDepartment of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, USA.
Ying YanEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Maneesh JainDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Apar K GantiDepartment of Medicine, VA Nebraska Western Iowa Health Care System, Omaha, NE, USA.
Moorthy P PonnusamyDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Surinder K BatraDepartment of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
University of Nebraska Medical Center · US

Funding

Tissue CoreP50CA127297 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI SINGH, PANKAJ KUMAR · 2008 to 2018
$17.1M
Early Diagnosis of Pancreatic CancerU01CA111294 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K., HOLLINGSWORTH, MICHAEL A. · 2004 to 2015
$7.1M
Role of N-Cadherin in Pancreatic Tumor MicroenvironmentU54CA163120 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI HOLLINGSWORTH, MICHAEL A. · 2011 to 2015
$4.2M
Smoking and pancreatic cancerR01CA133774 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2008 to 2012
$1.8M
Targeting Mucin and EGFR Axis in Pancreatic CancerR01CA183459 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2014 to 2018
$1.6M
Molecular Markers for the Diagnosis of Pancreatic CancerR01CA131944 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2008 to 2012
$1.5M
PD2/Paf1 and pancreatic cancer stem cellsK22CA175260 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PONNUSAMY, MOORTHY P. · 2014 to 2016
$364k
Targeting MUC4 for chemosensitization of pancreatic cancerR03CA167342 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BATRA, SURINDER K. · 2012 to 2013
$143k
NCI NIH HHS 5R03CA167342NCI NIH HHS K22 CA175260NCI NIH HHS P50 CA127297NCI NIH HHS R01 CA131944NCI NIH HHS R01 CA133774NCI NIH HHS R01 CA183459NCI NIH HHS R03 CA167342NCI NIH HHS U01 CA111294NCI NIH HHS U54 CA163120
6 · The paper itself

Abstract

Several studies have demonstrated that MUC4 is involved in progression and metastasis of pancreatic cancer (PC). Here, we report that HER3/MUC4 interaction in HER2 low cells is critical in driving pancreatic tumorigenesis. Upon HER2 knockdown, we observed elevated expression of HER3 and MUC4 and their interactions, which was confirmed by immunoprecipitation and bioinformatics analyses. In paired human PC tissues, higher percentage of HER3 positivity (10/33, 30.3%; p = 0.001) was observed than HER2 (5/33, 15.1%; p = 0.031), which was further confirmed in spontaneous mice (KPC; KrasG12D; Trp53R172H/+; Pdx-Cre) tumors of different weeks. Mechanistically, increased phosphorylation of ERK and expression of PI3K and c-Myc were observed in HER2 knockdown cells, suggesting a positive role for HER3/MUC4 in HER2 low cells. Further, HER2 knockdown resulted in increased proliferation, motility and tumorigenicity of PC cells. Consistently, transient knockdown of HER3 by siRNA in HER2 knockdown cells led to decreased proliferation. These observations led us to conclude that HER3 interacts with MUC4 to promote proliferation in HER2 low PC cells. Further, deficiency of both HER2 and HER3 leads to decreased proliferation of PC cells. Hence targeting these newly identified HER3/MUC4 signals would improve the PC patients survival by intercepting MUC4 mediated oncogenic signaling.

Indexed as

Gene Expression Regulation, NeoplasticAmino Acid SequenceAnimalsCarcinogenesisCell CycleCell ProliferationDisease ProgressionErb-b2 Receptor Tyrosine KinasesFemaleHumansMiceMice, NudeMolecular Sequence DataMucin-4Neoplasm MetastasisNeoplasm TransplantationERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesERBB3 protein, humanMUC4 protein, humanMucin-4Phosphatidylinositol 3-KinasesProto-Oncogene Proteins c-mycReceptor, ErbB-3HER2HER3KPC modelMUC4pancreatic cancer

Identifiers

PMID26035354
PMCPMC4673252
OpenAlexW2114024778

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.