Evidence map›Paper›PMID 25088198›Full record

ArticleOncogene2015

Sequestosome 1/p62 facilitates HER2-induced mammary tumorigenesis through multiple signaling pathways.

X Cai-McRae, H Zhong, V Karantza

Open access · bronzeAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.6field-weighted citation impact, top 19% 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

21 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
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  4. Review
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  7. Article
  8. Potential Applications of NRF2 Inhibitors in Cancer Therapy.Oxidative medicine and cellular longevity · 2019
    Review
  9. Autophagic Regulation of p62 is Critical for Cancer Therapy.International journal of molecular sciences · 2018
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Oncosuppressive functions of decorin.Molecular & cellular oncology
    Review
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

3 authors at 1 institution in 1 country.

X Cai-McRae1] Rutgers, The State University of New Jersey, New Brunswick, NJ, USA [2] Department of Medicine-Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.
H Zhong1] Department of Medicine-Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA [2] Department of Pathology and Laboratory Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
V Karantza1] Rutgers, The State University of New Jersey, New Brunswick, NJ, USA [2] Department of Medicine-Medical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA [3] Division of Medical Oncology, Department of Internal Medicine, Rutgers Robert Wood Johnson Medical School, Piscataway, NJ, USA.
Rutgers, The State University of New Jersey · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Previous studies have shown that increased levels of the adaptor protein Sequestosome 1/p62 are observed in human breast cancers and significantly correlate with HER2 overexpression. However, the role of p62 in the pathophysiology of HER2-induced mammary tumorigenesis has not yet been investigated. In this study, we report that p62 facilitates HER2-mediated cell survival in both two-dimensional and three-dimensional cell culture and that HER2-induced cellular transformation requires p62, as well as NRF2, which is known to become stabilized by its release from Kelch-like ECH-associated protein 1 (KEAP1) via p62-KEAP1 interaction. In agreement with these results, genetic ablation of p62 delays HER2-induced mammary tumorigenesis in tumor cell allografts in nude mice, and in MMTV-Neu transgenic mice. We also report that ablation of p62 impairs AKT and β-catenin activation in association with PTEN (phosphatase and tensin homolog deleted on chromosome ten) accumulation, both in vitro and in vivo. Further in vivo studies suggest that loss of p62 also impairs NF-κB and NRF2 activation. Collectively, our results provide compelling evidence that p62 contributes to HER2-induced mammary tumorigenesis through multiple signaling pathways, including the PTEN/phosphoinositide-3-kinase/AKT axis, WNT/β-catenin signaling, the NF-κB pathway and the NRF2-KEAP1 axis, and offer novel insights into the potential role of p62 in the regulation of the tumor suppressor PTEN.

Indexed as

Signal TransductionAdaptor Proteins, Signal TransducingAnimalsBreast NeoplasmsCell Culture TechniquesCell Line, TumorCell SurvivalCell Transformation, NeoplasticErb-b2 Receptor Tyrosine KinasesFemaleHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1MCF-7 CellsMiceMice, NudeAdaptor Proteins, Signal TransducingERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesIntracellular Signaling Peptides and ProteinsKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2PTEN PhosphohydrolasePTEN protein, humanSequestosome-1 ProteinSQSTM1 protein, human

Identifiers

PMID25088198
OpenAlexW1993287255

What OpenQuestion holds

Textmetadata
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.