Evidence map›Paper›PMID 38421310›Full record

ArticleCancer research communications2024

Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail.

Mysore S Veena, Jungmo J Gahng, Mustafa Alani, Albert Y Ko, Saroj K Basak, Isabelle Y Liu, Kimberly J Hwang, Jenna R Chatoff, Natarajan Venkatesan, Marco Morselli and 12 more

Open access · goldAbstract read
In one paragraph

Article in Cancer research communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact, top 98% 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

0 citing papers in PubMed, 0 citations in OpenAlex.

No citing paper in PubMed yet.

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

22 authors at 6 institutions in 2 countries.

Mysore S VeenaDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0008-3168-8027
Jungmo J GahngDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0001-6288-2158
Mustafa AlaniDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0001-2128-9144
Albert Y KoDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0004-3435-1754
Saroj K BasakDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0001-7577-4543
Isabelle Y LiuDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0007-9980-5579
Kimberly J HwangDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0002-7884-5954
Jenna R ChatoffDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0009-9806-2763
Natarajan VenkatesanDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0008-1030-1532
Marco MorselliDepartment of Molecular, Cellular and Developmental Biology, UCLA, Los Angeles, California.ORCID 0000-0003-3351-5791
Weihong YanDepartment of Chemistry and Biochemistry and the Institute for Quantitative and Computational Biology, UCLA, Los Angeles, California.ORCID 0009-0003-0999-4785
Ibraheem AliDepartment of Louise M. Darling Biomedical Library and The Institute for Quantitative and Computational Biology, UCLA, Los Angeles, California.ORCID 0000-0003-3945-2701
Karolina Elżbieta Kaczor-UrbanowiczDepartment of Oral Biology and Medicine, Center for Oral and Head/Neck Oncology Research, School of Dentistry, UCLA, Los Angeles, California.ORCID 0000-0001-9243-3652
Bhavani Shankara GowdaDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0009-0002-5264-9058
Patrick FrostDepartment of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0003-3348-5983
Matteo PellegriniDepartment of Molecular, Cellular and Developmental Biology, UCLA, Los Angeles, California.ORCID 0000-0001-9355-9564
Neda A MoatamedDepartment of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0002-9986-8058
Sharon P WilczynskiDepartment of Pathology, City of Hope National Medical Center, Duarte, California.ORCID 0009-0004-3063-786X
Pascale BomontERC team, INMG, UCBL Lyon1 - CNRS UMR5261 - INSERM U1315, Université Lyon 1, Université de Lyon, Lyon, France.ORCID 0000-0001-7216-3261
Marilene B WangDepartment of Surgery, VAGLAHS and Department of Head and Neck Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0002-2799-6325
Daniel Sanghoon ShinDepartment of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0002-3784-5336
Eri S SrivatsanDepartment of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California.ORCID 0000-0001-5551-8163
University of California, Los Angeles · USCity Of Hope National Medical Center · USQB3 · USUCLA Health · USUniversité Claude Bernard Lyon 1 · FRWest Los Angeles College · US

Funding

Targeting the in Vivo Hypoxic Microenvironment of Multiple Myeloma as an Anti-Tumor StrategyI01BX004280 · VA · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · PI FROST, PATRICK J · 2019 to 2022
–
BLRD VA I01 BX004280
6 · The paper itself

Abstract

Gigaxonin is an E3 ubiquitin ligase that plays a role in cytoskeletal stability. Its role in cancer is not yet clearly understood. Our previous studies of head and neck cancer had identified gigaxonin interacting with p16 for NFκB ubiquitination. To explore its role in cancer cell growth suppression, we analyzed normal and tumor DNA from cervical and head and neck cancers. There was a higher frequency of exon 8 SNP (c.1293 C>T, rs2608555) in the tumor (46% vs. 25% normal, P = 0.011) pointing to a relationship to cancer. Comparison of primary tumor with recurrence and metastasis did not reveal a statistical significance. Two cervical cancer cell lines, ME180 and HT3 harboring exon 8 SNP and showing T allele expression correlated with higher gigaxonin expression, reduced in vitro cell growth and enhanced cisplatin sensitivity in comparison with C allele expressing cancer cell lines. Loss of gigaxonin expression in ME180 cells through CRISPR-Cas9 or siRNA led to aggressive cancer cell growth including increased migration and Matrigel invasion. The in vitro cell growth phenotypes were reversed with re-expression of gigaxonin. Suppression of cell growth correlated with reduced Snail and increased e-cadherin expression. Mouse tail vein injection studies showed increased lung metastasis of cells with low gigaxonin expression and reduced metastasis with reexpression of gigaxonin. We have found an association between C allele expression and RNA instability and absence of multimeric protein formation. From our results, we conclude that gigaxonin expression is associated with suppression of epithelial-mesenchymal transition through inhibition of Snail. SIGNIFICANCE: Our results suggest that GAN gene exon 8 SNP T allele expression correlates with higher gigaxonin expression and suppression of aggressive cancer cell growth. There is downregulation of Snail and upregulation of e-cadherin through NFκB ubiquitination. We hypothesize that exon 8 T allele and gigaxonin expression could serve as diagnostic markers of suppression of aggressive growth of head and neck cancer.

Indexed as

Head and Neck NeoplasmsAnimalsCadherinsCell Line, TumorDown-RegulationEpithelial-Mesenchymal TransitionHumansMiceCadherins

Identifiers

PMID38421310
PMCPMC10921914
OpenAlexW4392284744

What OpenQuestion holds

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LicenceCC BY
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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.