Evidence map›Paper›PMID 37995683›Full record

ArticleCancer cell2023

Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation.

Chia-Chun Chen, Wendy Tran, Kai Song, Tyler Sugimoto, Matthew B Obusan, Liang Wang, Katherine M Sheu, Donghui Cheng, Lisa Ta, Grigor Varuzhanyan and 15 more

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

Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 1 pooled it
15.6field-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

54 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.

  1. Pooled it
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  10. Synthetic lethality between RB-loss and E2F3 inhibition in small cell cancers targeted by pyrimidine synthesis blockade.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  11. Article
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  15. RUNX1T1 drives stem-like small-cell neuroendocrine prostate cancer identity.Frontiers in cell and developmental biology · 2026
    Article
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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

25 authors at 7 institutions in 2 countries.

Chia-Chun ChenDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Wendy TranDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Kai SongDepartment of Bioengineering, UCLA, Los Angeles, CA, USA.
Tyler SugimotoDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Matthew B ObusanDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Liang WangDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Katherine M SheuDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Donghui ChengEli and Edythe Broad Stem Cell Research Center, UCLA, Los Angeles, CA, USA.
Lisa TaDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Grigor VaruzhanyanDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Arthur HuangDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Runzhe XuDepartment of Biological Chemistry, UCLA, Los Angeles, CA, USA.
Yuanhong ZengDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Amirreza BorujerdpurDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Nicholas A BayleyDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Miyako NoguchiDepartment of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA.
Zhiyuan MaoDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Colm MorrisseyDepartment of Urology, University of Washington School of Medicine, Seattle, WA, USA.
Eva CoreyDepartment of Urology, University of Washington School of Medicine, Seattle, WA, USA.
Peter S NelsonDivision of Human Biology, Fred Hutchinson Cancer Center, Seattle, WA, USA; Division of Clinical Research, Fred Hutchinson Cancer Center, Seattle, WA, USA; Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA.
Yue ZhaoDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA; Department of Pathology, College of Basic Medical Sciences and the First Hospital, China Medical University, Shenyang, China.
Jiaoti HuangDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Jung Wook ParkDepartment of Pathology, Duke University School of Medicine, Durham, NC, USA.
Owen N WitteDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Microbiology, Immunology, and Molecular Genetics, UCLA, Los Angeles, CA, USA; Eli and Edythe Broad Stem Cell Research Center, UCLA, Los Angeles, CA, USA; Molecular Biology Institute, UCLA, Los Angeles, CA, USA; Parker Institute for Cancer Immunotherapy, UCLA, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA. Electronic address: owenwitte@mednet.ucla.edu.
Thomas G GraeberDepartment of Molecular and Medical Pharmacology, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, USA; Crump Institute for Molecular Imaging, UCLA, Los Angeles, CA, USA; California NanoSystems Institute, UCLA, Los Angeles, CA, USA; Metabolomics Center, UCLA, Los Angeles, CA, USA. Electronic address: tgraeber@mednet.ucla.edu.
University of California, Los Angeles · USUniversity of Washington · USUCLA Health · USBroad Center · USDuke University · USFirst Hospital of China Medical University · CNLa Jolla Bioengineering Institute · US

Funding

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
UCLA-Caltech Medical Scientist Training ProgramT32GM008042 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI AJIJOLA, OLUJIMI A, DAWSON, DAVID WAYNE · 1985 to 2023
$29.9M
UCLA SPORE in Brain CancerP50CA211015 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Yvonne Yu-Hsuan Chen · 2017 to 2026
$25.2M
Steroid Metabolism in Castration-Resistant Prostate CancerP01CA163227 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PETER S NELSON · 2013 to 2026
$25.0M
TUMOR CELL SURFACES AND CHROMOSOMEST32CA009056 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Gay M Crooks, David A. Nathanson · 1985 to 2026
$10.5M
Multi-omic analysis of Myc-driven splicing for prostate cancer therapeutic developmentR01CA220238 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BLACK, DOUGLAS L, WITTE, OWEN N. · 2018 to 2022
$3.2M
Targeting Genomic Instability in Lethal Neuroendocrine Prostate CancerR01CA222877 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GRAEBER, THOMAS G, WITTE, OWEN N. · 2018 to 2022
$2.6M
Defining and Targeting Lineage Transition Programs Operative in AR Pathway Independent Prostate CancerR01CA234715 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI NELSON, PETER S · 2020 to 2024
$2.0M
NCI NIH HHS P01 CA163227NCI NIH HHS P50 CA092131NCI NIH HHS P50 CA097186NCI NIH HHS P50 CA211015NCI NIH HHS R01 CA220238NCI NIH HHS R01 CA222877NCI NIH HHS R01 CA234715NCI NIH HHS T32 CA009056NIGMS NIH HHS T32 GM008042
6 · The paper itself

Abstract

Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2. Temporal regulation by groups of transcription factors across developmental stages reveals that cellular reprogramming precedes the induction of neuronal programs. TFAP4 and ASCL1/2 feedback are identified as potential regulators of ASCL1 and ASCL2 expression. Our study provides temporal transcriptional patterns and uncovers pan-tissue parallels between prostate and lung cancers, as well as connections to normal neuroendocrine cell states.

Indexed as

Carcinoma, Small CellLung NeoplasmsProstatic NeoplasmsSmall Cell Lung CarcinomaBasic Helix-Loop-Helix ProteinsCell Line, TumorCell TransdifferentiationGene Expression Regulation, NeoplasticHumansMaleTranscription FactorsASCL2 protein, humanBasic Helix-Loop-Helix ProteinsTranscription FactorsASCL1ASCL2cancerlineage plasticityneuroendocrinePOU2F3, TFAP4prostatesmall cellstem-liketrans-differentiation

Identifiers

PMID37995683
PMCPMC10878415
OpenAlexW4388915239

What OpenQuestion holds

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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.