Evidence map›Paper›PMID 40738412›Full record

ArticleCancer letters2025

ECD co-operates with ERBB2 to promote tumorigenesis through upregulation of unfolded protein response and glycolysis.

Benjamin B Kennedy, Mohsin Raza, Sameer Mirza, Asher Rajkumar Rajan, Farshid Oruji, Matthew M Storck, Subodh M Lele, Timothy E Reznicek, Lusheng Li, M Jordan Rowley and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancer letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Benjamin B KennedyDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Mohsin RazaDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Sameer MirzaDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Asher Rajkumar RajanDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Farshid OrujiDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Matthew M StorckEppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Subodh M LeleDepartment of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Timothy E ReznicekDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Lusheng LiDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
M Jordan RowleyDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Shibiao WanDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA.
Bhopal C MohapatraDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: bmohapat@unmc.edu.
Hamid BandDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: hband@unmc.edu.
Vimla BandDepartment of Genetics, Cell Biology, and Anatomy, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA. Electronic address: vband@unmc.edu.

Funding

Fine-Scale Genome Folding Relative to Transcription and LocationR35GM147467 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Michael Jordan Rowley · 2022 to 2026
$2.0M
Ecdysoneless, A Novel Regulator of Androgen ReceptorR21CA241055 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2019 to 2020
$379k
Co-Oncogenic Role of ECD in HER2-Driven Breast CancerR03CA253193 · NCI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI BAND, VIMLA · 2021 to 2022
$153k
NCI NIH HHS R03 CA253193NCI NIH HHS R21 CA241055NIGMS NIH HHS R35 GM147467
6 · The paper itself

Abstract

The ecdysoneless (ECD) mRNA and protein are overexpressed in breast cancer (BC), correlating with poor prognosis and shorter patient survival, particularly in ERBB2/HER2-positive BC. This study investigates the co-operative oncogenic mechanism of ECD and ERBB2 by deriving transgenic mice overexpressing ECD and/or ERBB2 (huHER2) in mammary epithelium under the MMTV promoter, as well as immortal human mammary epithelial cell lines (hMECs) overexpressing ECD and/or ERBB2. While the tumor latency and percentage of mice with tumors were similar between single and double-transgenic mice, we observed more and larger tumors in double transgenic mice in comparison to ECD or huHER2 single transgenic mice. Compared to huHER2Tg mice, which developed more homogenous solid nodular carcinomas, double transgenic mice (ECD;huHER2Tg) developed heterogenous and histologically aggressive mammary tumors with basal-like phenotype and epithelial mesenchymal transition (EMT) features, as seen in ECDTg mice and those reported in patients. ECD and ERBB2 overexpressing hMECs showed significant increase in oncogenic traits as compared to single gene expressing cells. Transcriptomic analysis revealed upregulation of two major oncogenic pathways, unfolded protein response (UPR) and glycolysis in ECD;huHER2Tg tumors as well as in ECD + ERBB2-overexpressing hMECs. ECD + ERBB2-overexpressing hMECs exhibited an increase in glucose uptake and enhanced glycolytic rate as compared to ECD or ERBB2-overexpressing hMECs. ECD as an RNA binding protein directly associated with mRNAs of three key glycolytic enzymes (LDHA, PKM2 and HK2) and mRNA of a major UPR regulated gene HSPA5, and increased mRNA stability. Knockdown of these genes resulted in decreased oncogenic traits of ECD + ERBB2 overexpressing hMECs. Taken together, our findings support a co-operative role of ECD and ERBB2 in oncogenesis by enhancing two major oncogenic pathways, UPR and glycolysis.

Indexed as

Erb-b2 Receptor Tyrosine KinasesGlycolysisUnfolded Protein ResponseAnimalsCarcinogenesisCell Line, TumorEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHumansMiceMice, TransgenicUp-RegulationERBB2 protein, humanErbb2 protein, mouseErb-b2 Receptor Tyrosine KinasesECDERBB2Glycolysis and mRNA stabilityhMECsMammary tumorstransgenic miceUPR

Identifiers

PMID40738412
PMCPMC13181842

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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.