Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer
Por:
Rodríguez-Hernández MA, Cruz-Ojeda P, López-Grueso MJ, Navarro-Villarán E, Requejo-Aguilar R, Castejón-Vega B, Negrete M, Gallego P, Vega-Ochoa Á, Victor VM, Cordero MD, Del Campo JA, Bárcena JA, Padilla CA and Muntané J
Publicada:
1 sep 2020
Ahead of Print:
23 may 2020
Resumen:
Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages.
There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.
Filiaciones:
Rodríguez-Hernández MA:
Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Cruz-Ojeda P:
Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
López-Grueso MJ:
Department of Biochemistry and Molecular Biology, University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
Navarro-Villarán E:
Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Requejo-Aguilar R:
Department of Biochemistry and Molecular Biology, University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
Castejón-Vega B:
Research Laboratory, Oral Medicine Department, University of Seville, Seville, Spain
Negrete M:
Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
Gallego P:
Unit for the Clinical Management of Digestive Diseases, Hospital University "Nuestra Señora de Valme", Sevilla, Spain
Vega-Ochoa Á:
Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
:
Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Service of Endocrinology and Nutrition, Hospital University "Doctor Peset", Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain
Department of Physiology, University of Valencia, Valencia, Spain
Cordero MD:
Research Laboratory, Oral Medicine Department, University of Seville, Seville, Spain
Department of Physiology, Institute of Nutrition and Food Technology "José Mataix", Biomedical Research Center (CIBM), University of Granada, Armilla, Spain
Del Campo JA:
Unit for the Clinical Management of Digestive Diseases, Hospital University "Nuestra Señora de Valme", Sevilla, Spain
Bárcena JA:
Department of Biochemistry and Molecular Biology, University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
Padilla CA:
Department of Biochemistry and Molecular Biology, University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain
Muntané J:
Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain
Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
Department of General Surgery, Hospital University "Virgen del Rocío"/IBiS/CSIC/University of Seville, Seville, Spain
Green Published, gold, Green Accepted
|