{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T11:57:32Z","timestamp":1792065452768,"version":"4.4.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Triple-negative breast cancer (TNBC) cells face metabolic, proteotoxic and treatment-associated stress, but the mechanisms that determine how stressed cells dispose of intracellular cargo remain incompletely defined. We hypothesize that lysosomal stress shifts part of the autophagy-associated cargo burden from intracellular degradation towards extracellular release in small extracellular vesicle (sEV)-enriched fractions. The rationale integrates general evidence linking autophagy with EV biology with two model-specific observations: RIP1 involvement in Manzamine A-induced secretory autophagy in breast cancer cells and RASAL2-dependent modulation of Rab27a activity and autophagy-associated sEV release in MDA-MB-231 cells. These observations motivate the hypothesis but do not establish its generality across TNBC backgrounds or forms of lysosomal stress. We therefore regard RIPK1 as a candidate regulator whose role may depend on the stress context, whereas the RASAL2-Rab27a module is functionally supported but mechanistically unresolved. The model predicts that perturbing these components will alter time-resolved paired intracellular and extracellular measurements. A coordinated sequence of lysosomal and autophagic changes preceding vesicle-associated export, together with exclusion of cell-death-associated particle release, would support the model; stressor-restricted, arm-specific or injury-associated outcomes would require its revision.<\/jats:p>","DOI":"10.3389\/fonc.2026.1923547","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:28:01Z","timestamp":1789964881000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lysosomal-stress-driven cargo-fate switching between autophagic degradation and small extracellular vesicle release in triple-negative breast cancer: a hypothesis and theory article"],"prefix":"10.3389","volume":"16","author":[{"given":"Yuanpeng","family":"Liu","sequence":"first","affiliation":[{"name":"School of Medicine, Shandong Xiehe University","place":["Jinan, Shandong, 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