Evidence map›Paper›PMID 38244540›Full record

ArticleCell reports. Medicine2024

UCHL1 is a potential molecular indicator and therapeutic target for neuroendocrine carcinomas.

Shiqin Liu, Timothy Chai, Fernando Garcia-Marques, Qingqing Yin, En-Chi Hsu, Michelle Shen, Angus Martin Shaw Toland, Abel Bermudez, Alifiani B Hartono, Christopher F Massey and 20 more

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

Article in Cell reports. Medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
10.0field-weighted citation impact, top 1% 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

26 citing papers in PubMed, 27 citations in OpenAlex.

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  4. Biomedicines · 2026
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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

30 authors at 8 institutions in 2 countries.

Shiqin LiuDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiology, Stanford University, Palo Alto, CA, USA.
Timothy ChaiStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA.
Fernando Garcia-MarquesDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Qingqing YinDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
En-Chi HsuDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Michelle ShenDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiology, Stanford University, Palo Alto, CA, USA.
Angus Martin Shaw TolandDepartment of Pathology, Stanford University, Stanford, CA, USA.
Abel BermudezDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Alifiani B HartonoDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Christopher F MasseyDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Chung S LeeDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA.
Liwei ZhengDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Maya BaronDepartment of Pediatrics, Stanford University, Stanford, CA, USA; Department of Genetics, Stanford University, Stanford, CA, USA.
Caden J DenningDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Merve AslanDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Holly M NguyenDepartment of Urology, University of Washington, Seattle, WA, USA.
Rosalie NolleyDepartment of Urology, Stanford University, Stanford, CA, USA.
Amina ZoubeidiDepartment of Urologic Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Millie DasDepartment of Medicine, VA Palo Alto Health Care System, Palo Alto, CA, USA; Department of Medicine, Division of Oncology, Stanford University, Stanford, CA, USA.
Christian A KunderDepartment of Pathology, Stanford University, Stanford, CA, USA.
Brooke E HowittDepartment of Pathology, Stanford University, Stanford, CA, USA.
H Tom SohDepartment of Radiology, Stanford University, Palo Alto, CA, USA; Department of Electrical Engineering, Stanford University, Stanford, CA, USA.
Irving L WeissmanStanford Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA; Ludwig Center for Cancer Stem Cell Research and Medicine, Stanford University, Stanford, CA, USA.
Michael A LissDepartment of Urology, UT Health San Antonio, San Antonio, TX, USA.
Arnold I ChinDepartment of Urology, University of California, Los Angeles, Los Angeles, CA, USA.
James D BrooksDepartment of Urology, Stanford University, Stanford, CA, USA.
Eva CoreyDepartment of Urology, University of Washington, Seattle, WA, USA.
Sharon J PitteriDepartment of Radiology, Stanford University, Palo Alto, CA, USA.
Jiaoti HuangDepartment of Pathology, Duke University, Durham, NC, USA.
Tanya StoyanovaDepartment of Molecular and Medical Pharmacology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Radiology, Stanford University, Palo Alto, CA, USA; Department of Urology, University of California, Los Angeles, Los Angeles, CA, USA. Electronic address: tstoyanova@mednet.ucla.edu.
Stanford University · USPalo Alto University · USUniversity of California, Los Angeles · USUniversity of Washington · USDuke University · USThe University of Texas Health Science Center at San Antonio · USUniversity of British Columbia · CAVA Palo Alto Health Care System · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
TRANSCRIPTOME AND PROTEOME STRATIFICATION OF PROSTATE ADENOCARCINOMA PHENOTYPESP50CA097186 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI PETER S NELSON · 2002 to 2026
$58.1M
UCLA SPORE IN PROSTATE CANCERP50CA092131 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI REITER, ROBERT E · 2002 to 2023
$42.6M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
Stanford Molecular and Cellular Characterization LaboratoryU01CA196387 · NCI · STANFORD UNIVERSITY · PI BROOKS, JAMES D. · 2015 to 2020
$5.2M
Testing ATAD2 as a new therapeutic target for advanced prostate cancerR01CA287669 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Tanya I Stoyanova · 2024 to 2026
$2.8M
Elucidating the Role of Trop2 in Prostate CancerR37CA240822 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Tanya I Stoyanova · 2020 to 2026
$2.5M
Delineate the Role of GSTP1 in Advanced Prostate CancerR01CA274978 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Tanya I Stoyanova · 2023 to 2026
$1.8M
Elucidating the Role of UCHL1 in Aggressive Prostate CancerR01CA244281 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI STOYANOVA, TANYA I · 2020 to 2024
$1.8M
Targeting AXL to overcome resistance to taxanes and platinum-based therapy in castrate resistant and neuroendocrine prostate cancerR21CA245595 · NCI · STANFORD UNIVERSITY · PI BROOKS, JAMES D. · 2020 to 2021
$406k
NCI NIH HHS P01 CA163227NCI NIH HHS P30 CA016086NCI NIH HHS P50 CA092131NCI NIH HHS P50 CA097186NCI NIH HHS R01 CA244281NCI NIH HHS R01 CA274978NCI NIH HHS R01 CA287669NCI NIH HHS R21 CA245595NCI NIH HHS R37 CA240822NCI NIH HHS U01 CA196387
6 · The paper itself

Abstract

Neuroendocrine carcinomas, such as neuroendocrine prostate cancer and small-cell lung cancer, commonly have a poor prognosis and limited therapeutic options. We report that ubiquitin carboxy-terminal hydrolase L1 (UCHL1), a deubiquitinating enzyme, is elevated in tissues and plasma from patients with neuroendocrine carcinomas. Loss of UCHL1 decreases tumor growth and inhibits metastasis of these malignancies. UCHL1 maintains neuroendocrine differentiation and promotes cancer progression by regulating nucleoporin, POM121, and p53. UCHL1 binds, deubiquitinates, and stabilizes POM121 to regulate POM121-associated nuclear transport of E2F1 and c-MYC. Treatment with the UCHL1 inhibitor LDN-57444 slows tumor growth and metastasis across neuroendocrine carcinomas. The combination of UCHL1 inhibitors with cisplatin, the standard of care used for neuroendocrine carcinomas, significantly delays tumor growth in pre-clinical settings. Our study reveals mechanisms of UCHL1 function in regulating the progression of neuroendocrine carcinomas and identifies UCHL1 as a therapeutic target and potential molecular indicator for diagnosing and monitoring treatment responses in these malignancies.

Indexed as

Carcinoma, NeuroendocrineLung NeoplasmsSmall Cell Lung CarcinomaHumansMaleMembrane GlycoproteinsUbiquitin ThiolesteraseMembrane GlycoproteinsPOM121 protein, humanUbiquitin ThiolesteraseUCHL1 protein, humanneuroblastomaneuroendocrine carcinomasneuroendocrine prostate cancernuclear pore complexsmall cell lung cancerUCHL1

Identifiers

PMID38244540
PMCPMC10897521
OpenAlexW4391071364

What OpenQuestion holds

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LicenceCC BY-NC-ND
Read underepoch 390

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.