Mitochondrial division inhibitor (mdivi-1) induces extracellular matrix (ECM)-detachment of viable breast cancer cells by a DRP1-independent mechanism.

Autor: Silva-Pavez E; Facultad de Odontología y Ciencias de la Rehabilitación, Universidad San Sebastián, Bellavista, Bellavista 7, Recoleta, Santiago, Chile. eduardo.silva@uss.cl.; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile. eduardo.silva@uss.cl., Mendoza E; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Morgado-Cáceres P; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Ahumada-Castro U; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Bustos G; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Kangme-Encalada M; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., de Arbina AL; Biodonostia Health Research Institute, 20014, San Sebastián, Spain., Puebla-Huerta A; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Muñoz F; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile., Cereceda L; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.; Laboratory of Nano-Regenerative Medicine, Biomedical Research and Innovation Center (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile., Varas-Godoy M; Cancer Cell Biology Lab., Centro de Biología Celular y Biomedicina (CEBICEM), Facultad de Medicina y Ciencia, Universidad San Sebastián, Lota 2465, Santiago, Chile.; Centro Ciencia & Vida, Fundación Ciencia & Vida, Avenida Del Valle Norte 725, Huechuraba, Santiago, Chile.; Advanced Center for Chronic Diseases (ACCDiS), Faculty of Medicine, Universidad de Chile, Santos Dumont 964, Independencia, Santiago, Chile., Hidalgo Y; IMPACT, Center of Interventional Medicine for Precision and Advanced Cellular Therapy, Santiago, Chile.; Laboratory of Nano-Regenerative Medicine, Biomedical Research and Innovation Center (CIIB), Faculty of Medicine, Universidad de los Andes, Santiago, Chile., Cardenas JC; Center for Integrative Biology, Faculty of Sciences, Universidad Mayor, Camino la Pirámide 5750, Huechuraba, Santiago, Chile. julio.cardenas@umayor.cl.; Geroscience Center for Brain Health and Metabolism, Santiago, Chile. julio.cardenas@umayor.cl.; Buck Institute for Research on Aging, Novato, USA. julio.cardenas@umayor.cl.; Department of Chemistry and Biochemistry, University of California, Santa Barbara, USA. julio.cardenas@umayor.cl.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Jun 19; Vol. 14 (1), pp. 14178. Date of Electronic Publication: 2024 Jun 19.
DOI: 10.1038/s41598-024-64228-9
Abstrakt: Increasing evidence supports the hypothesis that cancer progression is under mitochondrial control. Mitochondrial fission plays a pivotal role in the maintenance of cancer cell homeostasis. The inhibition of DRP1, the main regulator of mitochondrial fission, with the mitochondrial division inhibitor (mdivi-1) had been associated with cancer cell sensitivity to chemotherapeutics and decrease proliferation. Here, using breast cancer cells we find that mdivi-1 induces the detachment of the cells, leading to a bulk of floating cells that conserved their viability. Despite a decrease in their proliferative and clonogenic capabilities, these floating cells maintain the capacity to re-adhere upon re-seeding and retain their migratory and invasive potential. Interestingly, the cell detachment induced by mdivi-1 is independent of DRP1 but relies on inhibition of mitochondrial complex I. Furthermore, mdivi-1 induces cell detachment rely on glucose and the pentose phosphate pathway. Our data evidence a novel DRP1-independent effect of mdivi-1 in the attachment of cancer cells. The generation of floating viable cells restricts the use of mdivi-1 as a therapeutic agent and demonstrates that mdivi-1 effect on cancer cells are more complex than anticipated.
(© 2024. The Author(s).)
Databáze: MEDLINE
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