Evidence map›Paper›PMID 31444413›Full record

ArticleOncogene2019

Nrf2 and SQSTM1/p62 jointly contribute to mesenchymal transition and invasion in glioblastoma.

Petri Pölönen, Ashik Jawahar Deen, Hanna M Leinonen, Henna-Kaisa Jyrkkänen, Suvi Kuosmanen, Mimmi Mononen, Ashish Jain, Tomi Tuomainen, Sanna Pasonen-Seppänen, Jaana M Hartikainen and 6 more

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PubMed Publisher
In one paragraph

Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.

0numbers the graph read from it
0cells of the map it votes in
61citing papers in PubMed
3.8field-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

61 citing papers in PubMed, 90 citations in OpenAlex.

  1. NRF2 signaling drives chemoresistance in NSCLC and glioblastoma.Molecular and cellular biochemistry · 2026
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1 more citing papers are in PubMed but not listed here.

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

16 authors at 4 institutions in 2 countries.

Petri PölönenInstitute of Biomedicine, School of Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Ashik Jawahar Deen *Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Hanna M Leinonen *Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Henna-Kaisa JyrkkänenDepartment of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Suvi KuosmanenDepartment of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Mimmi MononenDepartment of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Ashish JainInstitute of Medical Biology, University of Tromsø, 9037, Tromsø, Norway.
Tomi TuomainenDepartment of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Sanna Pasonen-SeppänenInstitute of Biomedicine, School of Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Jaana M HartikainenInstitute of Clinical Medicine, University of Eastern Finland, P. O. Box 1627, FIN-70211, Kuopio, Finland.
Arto MannermaaInstitute of Clinical Medicine, University of Eastern Finland, P. O. Box 1627, FIN-70211, Kuopio, Finland.
Matti NykterFaculty of Medicine and Life Sciences and BioMediTech Institute, University of Tampere, P. O. Box 100, FIN-33014, Tampere, Finland.
Pasi TaviInstitute of Biomedicine, School of Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Terje JohansenInstitute of Medical Biology, University of Tromsø, 9037, Tromsø, Norway.ORCID http://orcid.org/0000-0003-1451-9578
Merja HeinäniemiInstitute of Biomedicine, School of Medicine, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland.
Anna-Liisa LevonenDepartment of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, P.O. Box 1627, FIN-70211, Kuopio, Finland. anna-liisa.levonen@uef.fi.ORCID http://orcid.org/0000-0002-6575-2137
University of Eastern Finland · FIOslo University Hospital · NOTampere University · FIUiT The Arctic University of Norway · NO

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Accumulating evidence suggests that constitutively active Nrf2 has a pivotal role in cancer as it induces pro-survival genes that promote cancer cell proliferation and chemoresistance. The mechanisms of Nrf2 dysregulation and functions in cancer have not been fully characterized. Here, we jointly analyzed the Broad-Novartis Cancer Cell Line Encyclopedia (CCLE) and the Cancer Genome Atlas (TCGA) multi-omics data in order to identify cancer types where Nrf2 activation is present. We found that Nrf2 is hyperactivated in a subset of glioblastoma (GBM) patients, whose tumors display a mesenchymal subtype, and uncover several different mechanisms contributing to increased Nrf2 activity. Importantly, we identified a positive feedback loop between SQSTM1/p62 and Nrf2 as a mechanism for activation of the Nrf2 pathway. We also show that autophagy and serine/threonine signaling regulates p62 mediated Keap1 degradation. Our results in glioma cell lines indicate that both Nrf2 and p62 promote proliferation, invasion and mesenchymal transition. Finally, Nrf2 activity was associated with decreased progression free survival in TCGA GBM patient samples, suggesting that treatments have limited efficacy if this transcription factor is overactivated. Overall, our findings place Nrf2 and p62 as the key components of the mesenchymal subtype network, with implications to tumorigenesis and treatment resistance. Thus, Nrf2 activation could be used as a surrogate prognostic marker in mesenchymal subtype GBMs. Furthermore, strategies aiming at either inhibiting Nrf2 or exploiting Nrf2 hyperactivity for targeted gene therapy may provide novel treatment options for this subset of GBM.

Indexed as

Cell ProliferationEpithelial-Mesenchymal TransitionFeedback, PhysiologicalFemaleGene Expression Regulation, NeoplasticGlioblastomaHumansHuman Umbilical Vein Endothelial CellsKelch-Like ECH-Associated Protein 1MaleNeoplasm InvasivenessNF-E2-Related Factor 2Oxidative StressProgression-Free SurvivalProtein BindingSequestosome-1 ProteinKEAP1 protein, humanKelch-Like ECH-Associated Protein 1NFE2L2 protein, humanNF-E2-Related Factor 2Sequestosome-1 ProteinSQSTM1 protein, human

Identifiers

PMID31444413
OpenAlexW2969552557

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.