Evidence map›Paper›PMID 29945888›Full record

ArticleGenes & development2018

POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer.

Yu-Han Huang, Olaf Klingbeil, Xue-Yan He, Xiaoli S Wu, Gayatri Arun, Bin Lu, Tim D D Somerville, Joseph P Milazzo, John E Wilkinson, Osama E Demerdash and 4 more

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 281 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
281citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

281 citing papers in PubMed, 1 synthesis or guideline pooled it, 418 citations in OpenAlex.

  1. Pooled it
  2. Clinical Benefit From Immunotherapy in Patients With SCLC Is Associated With Tumor Capacity for Antigen Presentation.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2023
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  18. The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026
    Article
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221 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

14 authors at 3 institutions in 1 country.

Yu-Han HuangCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Olaf KlingbeilCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Xue-Yan HeCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Xiaoli S WuCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Gayatri ArunCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Bin LuCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Tim D D SomervilleCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Joseph P MilazzoCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
John E WilkinsonDepartment of Pathology, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Osama E DemerdashCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
David L SpectorCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Mikala EgebladCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Junwei ShiDepartment of Cancer Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Christopher R VakocCold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Cold Spring Harbor Laboratory · USUniversity of Michigan–Ann Arbor · USUniversity of Pennsylvania · US

Funding

Single-Cell Biology Shared ResourceP30CA045508 · NCI · COLD SPRING HARBOR LABORATORY · PI John Edward Moses · 1987 to 2026
$118.9M
VIRAL TRANSACTIVATIONP01CA013106 · NCI · COLD SPRING HARBOR LABORATORY · PI Camila dos Santos · 1985 to 2026
$116.8M
BET bromodomain inhibition as targeted therapy in acute myeloid leukemiaR01CA174793 · NCI · COLD SPRING HARBOR LABORATORY · PI VAKOC, CHRISTOPHER · 2013 to 2023
$5.5M
NCI NIH HHS P01 CA013106NCI NIH HHS P30 CA045508NCI NIH HHS R01 CA174793
6 · The paper itself

Abstract

Small cell lung cancer (SCLC) is widely considered to be a tumor of pulmonary neuroendocrine cells; however, a variant form of this disease has been described that lacks neuroendocrine features. Here, we applied domain-focused CRISPR screening to human cancer cell lines to identify the transcription factor (TF) POU2F3 (POU class 2 homeobox 3; also known as SKN-1a/OCT-11) as a powerful dependency in a subset of SCLC lines. An analysis of human SCLC specimens revealed that POU2F3 is expressed exclusively in variant SCLC tumors that lack expression of neuroendocrine markers and instead express markers of a chemosensory lineage known as tuft cells. Using chromatin- and RNA-profiling experiments, we provide evidence that POU2F3 is a master regulator of tuft cell identity in a variant form of SCLC. Moreover, we show that most SCLC tumors can be classified into one of three lineages based on the expression of POU2F3, ASCL1, or NEUROD1. Our CRISPR screens exposed other unique dependencies in POU2F3-expressing SCLC lines, including the lineage TFs SOX9 and ASCL2 and the receptor tyrosine kinase IGF1R (insulin-like growth factor 1 receptor). These data reveal POU2F3 as a cell identity determinant and a dependency in a tuft cell-like variant of SCLC, which may reflect a previously unrecognized cell of origin or a

Indexed as

Gene Expression Regulation, NeoplasticAnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationCell LineageCell Line, TumorHumansLungLung NeoplasmsMiceOctamer Transcription FactorsReceptor, IGF Type 1Small Cell Lung CarcinomaASCL1 protein, humanBasic Helix-Loop-Helix ProteinsNEUROD1 protein, humanOctamer Transcription FactorsPOU2F3 protein, humanReceptor, IGF Type 1enhancermaster regulatorPOU2F3small cell lung cancertuft cell

Identifiers

PMID29945888
PMCPMC6075037
OpenAlexW2810630532

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.