000165458 001__ 165458
000165458 005__ 20260108143204.0
000165458 0247_ $$2doi$$a10.3390/cancers12040920
000165458 0248_ $$2sideral$$a146778
000165458 037__ $$aART-2020-146778
000165458 041__ $$aeng
000165458 100__ $$aHernández-Reséndiz, Ileana
000165458 245__ $$aInhibition of Kv10.1 Channels Sensitizes Mitochondria of Cancer Cells to Antimetabolic Agents
000165458 260__ $$c2020
000165458 5060_ $$aAccess copy available to the general public$$fUnrestricted
000165458 5203_ $$aReprogramming of energy metabolism constitutes one of the hallmarks of cancer and is, therefore, an emerging therapeutic target. We describe here that the potassium channel Kv10.1, which is frequently overexpressed in primary and metastatic cancer, and has been proposed a therapeutic target, participates in metabolic adaptation of cancer cells through regulation of mitochondrial dynamics. We used biochemical and cell biological techniques, live cell imaging and high-resolution microscopy, among other approaches, to study the impact of Kv10.1 on the regulation of mitochondrial stability. Inhibition of Kv10.1 expression or function led to mitochondrial fragmentation, increase in reactive oxygen species and increased autophagy. Cells with endogenous overexpression of Kv10.1 were also more sensitive to mitochondrial metabolism inhibitors than cells with low expression, indicating that they are more dependent on mitochondrial function. Consistently, a combined therapy using functional monoclonal antibodies for Kv10.1 and mitochondrial metabolism inhibitors resulted in enhanced efficacy of the inhibitors. Our data reveal a new mechanism regulated by Kv10.1 in cancer and a novel strategy to overcome drug resistance in cancers with a high expression of Kv10.1.
000165458 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000165458 590__ $$a6.639$$b2020
000165458 591__ $$aONCOLOGY$$b51 / 241 = 0.212$$c2020$$dQ1$$eT1
000165458 592__ $$a1.818$$b2020
000165458 593__ $$aOncology$$c2020$$dQ1
000165458 593__ $$aCancer Research$$c2020$$dQ1
000165458 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000165458 700__ $$0(orcid)0000-0003-2645-3983$$aPacheu-Grau, David$$uUniversidad de Zaragoza
000165458 700__ $$aSánchez, Araceli
000165458 700__ $$aPardo, Luis A.
000165458 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000165458 773__ $$g12, 4 (2020), 920 [20 pp.]$$pCancers$$tCancers$$x2072-6694
000165458 8564_ $$s8264149$$uhttps://zaguan.unizar.es/record/165458/files/texto_completo.pdf$$yVersión publicada
000165458 8564_ $$s2524611$$uhttps://zaguan.unizar.es/record/165458/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000165458 909CO $$ooai:zaguan.unizar.es:165458$$particulos$$pdriver
000165458 951__ $$a2026-01-08-14:11:00
000165458 980__ $$aARTICLE