RT info:eu-repo/semantics/article
T1 Mitochondria sustain store-operated currents in colon cancer cells but not in normal colonic cells: reversal by non-steroidal anti-inflammatory drugs
A1 Hernández Morales, Miriam
A1 Sobradillo Luengo, Diego
A1 Valero, Ruth Ana
A1 Muñoz Conejero, Eva
A1 Ubierna, Daniel
A1 Moyer, Mary P.
A1 Núñez Llorente, Lucía
A1 Villalobos Jorge, Carlos
K1 Calcium
K1 Calcio
K1 Mitochondria
K1 Mitocondrias
K1 Colorectal cancer
K1 Cáncer colorrectal
AB Tumor cells undergo a critical remodeling of intracellular Ca2+ homeostasis that contribute to important cancer hallmarks. Store-operated Ca2+ entry (SOCE), a Ca2+ entry pathway modulated by mitochondria, is dramatically enhanced in colon cancer cells. In addition, most cancer cells display the Warburg effect, a metabolic switch from mitochondrial metabolism to glycolysis that provides survival advantages. Accordingly, we investigated mitochondria control of store-operated currents (SOCs) in two cell lines previously selected for representing human normal colonic cells and colon cancer cells. We found that, in normal cells, mitochondria are important for SOCs activity but they are unable to prevent current inactivation. In contrast, in colon cancer cells, mitochondria are dispensable for SOCs activation but are able to prevent the slow, Ca2+-dependent inactivation of SOCs. This effect is associated to increased ability of tumor cell mitochondria to take up Ca2+ due to increased mitochondrial potential (ΔΨ) linked to the Warburg effect. Consistently with this view, selected non-steroidal anti-inflammatory drugs (NSAIDs) depolarize mitochondria, inhibit mitochondrial Ca2+ uptake and promote SOC inactivation, leading to inhibition of both SOCE and cancer cell proliferation. Thus, mitochondria sustain store-operated currents in colon cancer cells but not in normal colonic cells and this effect is counteracted by selected NSAIDs providing a mechanism for cancer chemoprevention.
PB Impact Journals
SN 1949-2553
YR 2017
FD 2017
LK http://uvadoc.uva.es/handle/10324/45041
UL http://uvadoc.uva.es/handle/10324/45041
LA eng
NO Oncotarget, 2017, vol. 8. p. 55332-55352
NO Producción Científica
DS UVaDOC
RD 05-feb-2025