Evidence map›Paper›PMID 41013744›Full record

ArticleBiomarker research2025

NPC1 as a novel therapeutic target for induction of pyroptosis in cancers.

Chuanchao Zhang, Qiang Wang, Pan Su, Jianfei Qian, Qi Guo, Wei Wu, Rui Duan, Yufei Zhang, Youli Zu, Ling Zhong and 2 more

Abstract read
In one paragraph

Article in Biomarker research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–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

2 citing papers in PubMed.

  1. Review
  2. Review
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

12 authors.

Chuanchao Zhang *Center for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Qiang Wang *Center for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Pan SuCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Jianfei QianCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Qi GuoCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Wei WuCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Rui DuanCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Yufei ZhangCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA.
Youli ZuDepartment of Pathology and Genomic Medicine, Institute for Academic Medicine, Houston Methodist Research Institute, Houston, TX, USA.
Ling ZhongCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA. zhonglingr@126.com.
Liuling XiaoCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA. xiaoliuling@cqmu.edu.cn.
Qing YiCenter for Translational Research in Hematological Malignancies, Houston Methodist Cancer Center/Houston Methodist Research Institute, Houston, TX, USA. qyi@houstonmethodist.org.

Funding

Role of tumor microenvironment-derived cholesterol in CD8+ T-cell exhaustionR01CA239255 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI YI, QING · 2019 to 2023
$2.1M
Role of lipid metabolism in CD8+ T cell ferroptosisR01CA278787 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI Qing Yi · 2023 to 2026
$1.9M
Novel mechanism of induction of tumor pyroptosis by IL-9-secreting Tc9 cellsR01CA282099 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI Qing Yi · 2023 to 2026
$1.9M
Role of MIF in myeloma bone homing and drug responseR01CA211073 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI YI, QING · 2017 to 2021
$1.8M
A novel T-cell subset able to kill relapsed cancersR01CA200539 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI YI, QING · 2016 to 2020
$1.8M
Exploring the role and potential of anti-viral drugs to sensitize cancer cells to chemotherapyR01CA285203 · NCI · METHODIST HOSPITAL RESEARCH INSTITUTE · PI Qing Yi · 2024 to 2026
$1.4M
Cancer Prevention & Research Institute of Texas Recruitment of Established Investigator Award RR180044High-Impact/High-Risk Research Award RP210868NCI NIH HHS R01 CA200539NCI NIH HHS R01 CA211073NCI NIH HHS R01 CA239255NCI NIH HHS R01 CA278787NCI NIH HHS R01 CA282099NCI NIH HHS R01 CA285203
6 · The paper itself

Abstract

backgroundCholesterol metabolism reprogramming is a hallmark of cancer cells that exhibit cholesterol addiction by absorbing low-density lipoprotein (LDL) to generate cholesterol for growth. Yet the underlying mechanisms remain unclear.

methodsWe began by identifying Niemann-Pick C1 (NPC1) as a key cholesterol uptake gene linked to cancer progression through clinical data analysis. Using three tumor models, we showed that NPC1 promotes tumor growth by suppressing pyroptosis. Finally, we demonstrated that the NPC1 inhibitor U18666A effectively inhibits tumor growth, supporting its therapeutic potential.

resultsHere we report that NPC1, a key player in cholesterol transport, protects cancer cells from pyroptosis across multiple cancer types. NPC1 expression was highly elevated in human cancers and negatively correlated with patient survival. NPC1 deficiency led to reduced cancer growth and enhanced sensitivity to pyroptosis under pyroptotic stress. NPC1 protects cancer cells from pyroptosis by maintaining cholesterol homeostasis and facilitating LDL-mediated cholesterol uptake, leading to enhanced geranylgeranyl pyrophosphate synthesis for cancer cell survival. Moreover, NPC1 inhibitor U18666A induced cancer cell pyroptosis and was highly therapeutic, either alone or combined with chemotherapeutics, against human hematologic and solid cancers in xenograft mouse models.

conclusionThis study reveals that NPC1 may be a potential therapeutic target for the treatment of human cancers.

Indexed as

CancerCholesterolNPC1PyroptosisU18666A

Identifiers

PMID41013744
PMCPMC12465410

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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.