ArticleCell death & disease2026
Pictilisib and nutrient stress synergize to induce methuosis via PI(4,5)P
Xuefei Wang, Xiaolin Sang, Yuemei Wen, Xingming Liao, Jiao Liu, Tiezheng Zheng, Tianming Xing, Min Wang, Dong An, Xining Zhang and 4 more
Abstract read
In one paragraphArticle in Cell death & disease, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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14 authors.
Xuefei Wang *Cancer Institute, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Xiaolin Sang *Zhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.ORCID http://orcid.org/0000-0001-8154-2853 Yuemei WenInstitute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
Xingming LiaoInstitute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
Jiao LiuCancer Institute, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Tiezheng ZhengCancer Institute, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Tianming XingInstitute of Cancer Stem Cell, Dalian Medical University, Dalian, Liaoning, China.
Min WangCancer Institute, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Dong AnCancer Institute, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Xining ZhangCancer Institute, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China.
Xiuling LiKey Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China. lixiuling@dicp.ac.cn.ORCID http://orcid.org/0000-0002-6016-9516 Xinmiao LiangKey Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, Liaoning, China. liangxm@dicp.ac.cn.ORCID http://orcid.org/0000-0003-4394-4274 Pixu LiuZhejiang Key Laboratory of Intelligent Cancer Biomarker Discovery and Translation, First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China. pixuliu@wmu.edu.cn.ORCID http://orcid.org/0000-0003-4094-8245 Funding
National Natural Science Foundation of China (National Science Foundation of China) 82302981National Natural Science Foundation of China (National Science Foundation of China) 82372649National Natural Science Foundation of China (National Science Foundation of China) 82472708
6 · The paper itselfAbstract
Aberrant phosphatidylinositol 3-kinase (PI3K) activation drives many cancers, but PI3K inhibitors like Pictilisib often induce cytostasis rather than cytotoxicity, limiting their therapeutic potential. Here we demonstrate that PI3K inhibition combined with nutrient stress triggers methuosis, a non-apoptotic form of programmed cell death characterized by dysregulated macropinosomes. This response occurs selectively in PI3K-aberrant cancer cells that maintain macropinocytic uptake despite PI3K inhibition. Methuosis-associated vacuoles originate from macropinosomes that retain endosomal markers but fail to undergo lysosomal fusion. Active macropinocytic uptake is essential for methuosis, as demonstrated by suppression with EIPA and Bafilomycin A1, whereas the AKT inhibitor MK2206 has no effect, establishing that direct PI3K inhibition, rather than AKT signaling, is required. Mechanistically, PI3K blockade prevents conversion of phosphatidylinositol (4,5)-bisphosphate (PI(4,5)P
Indexed as
NeoplasmsNutrientsPhosphatidylinositol 4,5-DiphosphatePinocytosisStress, PhysiologicalAnimalsApoptosisCell Line, TumorHeterocyclic Compounds, 3-RingHumansMacrolidesMiceMice, NudePhosphatidylinositol 3-KinasesPhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-aktHeterocyclic Compounds, 3-RingMacrolidesMK 2206Phosphatidylinositol 3-KinasesPhosphatidylinositol 4,5-DiphosphatePhosphoinositide-3 Kinase InhibitorsProto-Oncogene Proteins c-akt
Identifiers
PMID42303628
PMCPMC13500832
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