Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer

Redox Biology

P de la Cruz-Ojeda¹  Beatriz Castejón-Vega¹  C. Alicia Padilla²  J. Antonio Bárcena³  José A. Del Campo⁴  María Negrete⁵  Elena Navarro-Villarán⁵  Álvaro Vega-Ochoa⁶  Mª José López-Grueso⁶  María A. Rodríguez-Hernández⁶  Raquel Requejo-Aguilar⁶  Mario D. Cordero⁶  Jordi Muntané⁷  Paloma Gallego⁷  Victor M. Victor⁸ 

[1] Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain;Department of Physiology, University of Valencia, Valencia, 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;Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain;Department of Biochemistry and Molecular Biology, University of Cordoba, Maimonides Biomedical Research Institute of Cordoba (IMIBIC), Cordoba, Spain;Institute of Biomedicine of Seville (IBiS), IBiS/Hospital University “Virgen del Rocío”/CSIC/University of Seville, Seville, Spain;Research Laboratory, Oral Medicine Department, University of Seville, Seville, Spain;Unit for the Clinical Management of Digestive Diseases, Hospital University “Nuestra Señora de Valme”, Sevilla, Spain;

关键词: Autophagy;    Cell death;    Endoplasmic reticulum stress;    mTOR;    Redox status;    PGC-1α;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown