Valor de la proteína STAT3 como factor pronóstico en el carcinoma renal de célula clara. Revisión sistemática

Lorenté, David; Trilla, E.; Meseguer, Anna; Arévalo, J.; Nemours, Stéphane; Planas, Jacques; Placer, J.; Celma, A.; Salvador, C.; Regis, Lucas; Schwartzmann, Iván; Moróte, Juan

doi:10.1016/j.acuro.2018.08.003

Cited by 14 publications

(3 citation statements)

References 15 publications

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“…This study unraveled the interactive signaling pathways involved in G6PD overexpression, including ROS, NF-κB, and pSTAT3. Each of these pathways has been well studied in the tumorigenesis and development of a series of human cancers [22,29,33,48]. ROS production and clearance are closely related to intracellular redox homeostasis and can be regulated by many factors.…”

Section: Discussionmentioning

confidence: 99%

“…ROS could stimulate continuous activation of pSTAT3, NF-κB and MAPK signals [19,[23][24][25], and promote the occurrence and development of various types of cancer, including RCC, shin cancer and lung cancer [19,26,27]. NF-κB signaling over-activation has been described to contribute to RCC cell migration and invasion [28], and the high expression level of pSTAT3 S727 is expected to be an independent prognostic molecule for ccRCC patients [29,30]. Moreover, the interactions between NF-κB and STAT3 signaling pathways were discovered in various physiological and pathological processes, such as B-cell activation [31], cancer cell starvation [32,33], and mitochondrial fusion [34,35].…”

Section: Introductionmentioning

confidence: 99%

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NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC

Zhang

Yang

et al. 2020

Cancer Cell Int

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Background Glucose 6-phosphate dehydrogenase (G6PD) serves key roles in cancer cell metabolic reprogramming, and has been reported to be involved in certain carcinogenesis. Previous results from our laboratory demonstrated that overexpressed G6PD was a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer. G6PD could stimulate ccRCC growth and invasion through facilitating reactive oxygen species (ROS)-phosphorylated signal transducer and activator of transcription 3 (pSTAT3) activation and ROS-MAPK-MMP2 axis pathway, respectively. However, the reasons for ectopic G6PD overexpression and the proliferation repressive effect of G6PD inhibition in ccRCC are still unclear. Methods The impact of ROS accumulation on NF-κB signaling pathway and G6PD expression was determined by real-time RT-PCR and Western blot in ccRCC cells following treatment with ROS stimulator or scavenger. The regulatory function of NF-κB signaling pathway in G6PD transcription was analyzed by real-time RT-PCR, Western blot, luciferase and ChIP assay in ccRCC cells following treatment with NF-κB signaling activator/inhibitor or lentivirus infection. ChIP and Co-IP assay was performed to demonstrate protein-DNA and protein–protein interaction of NF-κB and pSTAT3, respectively. MTS assay, human tissue detection and xenograft model were conducted to characterize the association between NF-κB, pSTAT3, G6PD expression level and proliferation functions. Results ROS-stimulated NF-κB and pSTAT3 signaling over-activation could activate each other, and exhibit cross-talks in G6PD aberrant transcriptional regulation. The underlying mechanism was that NF-κB signaling pathway facilitated G6PD transcription via direct DNA–protein interaction with p65 instead of p50. p65 and pSTAT3 formed a p65/pSTAT3 complex, occupied the pSTAT3-binding site on G6PD promoter, and contributed to ccRCC proliferation following facilitated G6PD overexpression. G6PD, pSTAT3, and p65 were highly expressed and positively correlated with each other in ccRCC tissues, confirming that NF-κB and pSTAT3 synergistically promote G6PD overexpression. Moreover, G6PD inhibitor exhibited tumor-suppressor activities in ccRCC and attenuated the growth of ccRCC cells both in vitro and in vivo. Conclusion ROS-stimulated aberrations of NF-κB and pSTAT3 signaling pathway synergistically drive G6PD transcription through forming a p65/pSTAT3 complex. Moreover, G6PD activity inhibition may be a promising therapeutic strategy for ccRCC treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC

Zhang

Yang

et al. 2020

Cancer Cell Int

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“…It was shown that pSTAT3 and NF-kB might regulate a range of tumorigenesis-related genes either synergistically or independently [107]. Overactivation of NF-kB signaling has been shown to promote RCC oncogenic transformation [108]. High pSTAT3 expression is anticipated to be an independent prognostic molecule for individuals with ccRCC [109,110].…”

Section: The Oncogenic Role Of G6pdmentioning

confidence: 99%

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

Meo

Lasorsa

Rutigliano

et al. 2022

IJMS

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Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.

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Análisis de la expresión nuclear de pSer727-STAT3 como factor pronóstico en pacientes con carcinoma renal de células claras

Lorenté

Arévalo

Salcedo

et al. 2020

Actas Urológicas Españolas

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Valor de la proteína STAT3 como factor pronóstico en el carcinoma renal de célula clara. Revisión sistemática

Cited by 14 publications

References 15 publications

NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC

NF-κB and pSTAT3 synergistically drive G6PD overexpression and facilitate sensitivity to G6PD inhibition in ccRCC

Renal Cell Carcinoma as a Metabolic Disease: An Update on Main Pathways, Potential Biomarkers, and Therapeutic Targets

Análisis de la expresión nuclear de pSer727-STAT3 como factor pronóstico en pacientes con carcinoma renal de células claras

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