NPC1 as a novel therapeutic target for induction of pyroptosis in cancers
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Le résumé fourni par la source
BACKGROUND: Cholesterol 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. METHODS: We 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. RESULTS: Here 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. CONCLUSION: This study reveals that NPC1 may be a potential therapeutic target for the treatment of human cancers.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- NPC1 as a novel therapeutic target for induction of pyroptosis in cancers
- Date Crossref
- 26/09/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Houston Methodist Center for Translational Research in Hematological Malignancies pays non établi dans la noticeÉtablissement de santé
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The Affiliated Yongchuan Hospital of Chongqing Medical University pays non établi dans la noticeÉtablissement de santé
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Chongqing Medical University pays non établi dans la noticeUniversité ou école supérieure
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Institute for Academic Medicine Department of Pathology and Genomic Medicine pays non établi dans la noticeStructure de recherche
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School of Basic Medicine Present address: First Affiliated Hospital pays non établi dans la noticeUniversité ou école supérieure
Center for Translational Research in Hematological Malignancies — Houston Methodist, The Affiliated Yongchuan Hospital of Chongqing Medical University et Chongqing Medical University, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.