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

Autor: Silva-Pavez, Eduardo, Mendoza, Elizabeth, Morgado-Cáceres, Pablo, Ahumada-Castro, Ulises, Bustos, Galdo, Kangme-Encalada, Matías, de Arbina, Amaia Lopez, Puebla-Huerta, Andrea, Muñoz, Felipe, Cereceda, Lucas, Varas-Godoy, Manuel, Hidalgo, Yessia, Cardenas, J. Cesar
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Zdroj: Scientific Reports; 6/19/2024, Vol. 14 Issue 1, p1-15, 15p
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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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