{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:49:28Z","timestamp":1791449368451,"version":"4.3.3"},"reference-count":68,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":43,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Perturbation of macropinocytosis triggers methuosis, a non\u2010apoptotic cell death characterized by cytoplasmic vacuolization. However, the regulatory mechanisms of methuosis remain poorly defined. Lipid metabolism dysregulation is implicated in various cell death pathways, while its role in methuosis has remained elusive. Herein, LXX\u20108250, an isopropanolamine derivative of \u03b2\u2010elemene, induced a vacuolization\u2010associated cell death in breast and liver cancer cell lines. This process was accompanied by massive macropinocytosis, thereby confirming the occurrence of methuosis. Mechanistically, hypoxia\u2010inducible lipid droplet\u2010associated protein (HILPDA), a key regulator that promotes intracellular triacylglycerol (TAG) accumulation, was identified as the direct target of LXX\u20108250. By suppressing HILPDA, LXX\u20108250 inhibited diacylglycerol O\u2010acyltransferase 1 (DGAT1) and activated adipose triglyceride lipase (ATGL). Consequently, lipid droplets and cellular TAG levels were reduced, while the subsequent increased diacylglycerol (DAG) stimulated macropinosome formation, leading to methuosis in these cells. In this study, we discover a novel methuosis agonist LXX\u20108250, and elucidate the critical role of HILPDA repression\u2010dysregulated lipid metabolism in methuosis. Our study highlighted the potential of targeting this pathway as a therapeutic strategy to trigger cancer cell death.<\/jats:p>","DOI":"10.1002\/biof.70142","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T02:32:07Z","timestamp":1786674727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>HILPDA<\/scp>\n                    Repression Induces Methuosis in Breast and Liver Cancer Cells by Dysregulating Lipid Metabolism"],"prefix":"10.1002","volume":"52","author":[{"given":"Jie","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, College of Basic Medical Sciences Dalian Medical University  Dalian People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuanxin","family":"Zhai","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, College of Basic Medical Sciences Dalian 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