The role of STAT3 protein as a prognostic factor in the clear cell renal carcinoma. Systematic review

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

doi:10.1016/j.acuroe.2019.02.006

Cited by 8 publications

(9 citation statements)

References 20 publications

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“…Constitutively activated pY-STAT3 seems to control oncogenic functions of most tumor cells (Bharadwaj et al, 2016b). Exceptionally, pS-STAT3, and not pY-STAT3, seems to be oncogenic in metastatic clear cell renal cell carcinoma (Lorente et al, 2019) and chronic lymphocytic leukemia (CLL) (Frank et al, 1997;Hazan-Halevy et al, 2010;Lupardus et al, 2014;Antosz et al, 2015;Rozovski et al, 2016Rozovski et al, , 2017aKondo et al, 2018). CK2, in the presence of increased levels of CD5 and B cell linker protein, both of which are low to absent in normal B cells, phosphorylates STAT3 at S727 (Rozovski et al, 2015) in CLL cells.…”

Section: A Canonical Janus Kinase/signal Transducer and Activator Ofmentioning

confidence: 99%

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

et al. 2020

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Section: A Canonical Janus Kinase/signal Transducer and Activator Ofmentioning

confidence: 99%

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

et al. 2020

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“…ROS could stimulate continuous activation of pSTAT3, NF-κB and MAPK signals [ 19 , 23 – 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%

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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“…786-O cells and Caki-1 cells were inoculated into six-well plates (140675; Thermo Scientific) at 3×10 5 cells per well and incubated overnight. After that, the original culture medium was replaced with DMEM containing mitomycin (10 µg/mL).…”

Section: Wound-healing Testmentioning

confidence: 99%

“…Unfortunately, the major cause of death for most ccRCC patients is the metastasis and recurrence of tumor cells [3]. Several new biomarkers have been explored to diagnose and predict the occurrence and development of ccRCC [4][5][6].…”

Section: Introductionmentioning

confidence: 99%

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

Zhou

Wang

Qiu

et al. 2020

Preprint

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Background: Clear cell renal cell carcinoma (ccRCC) is the most common form of adult kidney cancer. Ubiquitin-specific protease (USP)44 has been reported to be involved in various cancers. We investigated the function, role and molecular mechanism of USP44 in ccRCC. Methods: Data obtained from the Cancer Genome Atlas Data Portal and Gene Expression Omnibus database were analyzed to uncover the clinical relevance of USP44 expression and tumor development. USP44 function in the proliferation and migration of tumor cells was assessed by cellular and molecular analyses using ccRCC lines (786-O cells and Caki-1 cells). Results: USP44 showed low expression in ccRCC cancer tissues compared with that in normal tissue. USP44 expression was negatively correlated with tumor stage, tumor grade, and patient survival . USP44 overexpression inhibited the proliferation and migration of 786-O cells and Caki-1 cells significantly. USP44 overexpression also prohibited cell proliferation by upregulating expression of P21, downregulating cyclin-D1 expression, and inhibiting cell migration by upregulating expression of matrix metalloproteinase (MMP)2 and MMP9. USP44 knockdown enhanced the proliferation and migration of 786-O cells and Caki-1 cells. USP44 function in inhibiting the proliferation and migration of 786-O cells and Caki-1 cells was associated with phosphorylation of Jun N-terminal kinase (JNK). Conclusion: USP44 may be a marker in predicting ccRCC progression. Inhibition by USP44 of the proliferation and migration of 786-O cells and Caki-1 cells is dependent upon the JNK pathway.

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The role of STAT3 protein as a prognostic factor in the clear cell renal carcinoma. Systematic review

Cited by 8 publications

References 20 publications

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 to Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution

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

Ubiquitin-specific protease-44 inhibits the proliferation and migration of cells via inhibition of JNK pathway in clear cell renal cell carcinoma

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