ERCC6L that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating MAPK signalling pathway

Zhang, Gejun; Yu, Zi; Fu, Shui; Lv, Chengcheng; Dong, Qingzhuo; Fu, Cheng; Kong, Chuize; Zeng, Yu

doi:10.1038/s41417-018-0064-8

Cited by 19 publications

(19 citation statements)

References 34 publications

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“…Furthermore, a case-control study and meta-analysis demonstrated that increased MMP2 protein expression is positively correlated with tumor metastasis (52,53). The MAPK signaling pathway is largely implicated in the progression and metastasis of various types of cancer, including RCC (54,55). The p38/MAPK, ERK/MAPK and JNK/MAPK cascades are commonly involved in the malignant progression of RCC (56,57).…”

Section: Discussionmentioning

confidence: 99%

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

et al. 2020

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Glucose-6-phosphate dehydrogenase (G6PD) is crucial rate-limiting enzyme of the pentose phosphate pathway (PPP). G6PD dysregulation has been reported in various types of human cancer, and the role of G6PD in cancer progression was demonstrated in numerous studies. A previous study from our laboratory described the prognostic significance of G6PD in clear cell renal cell carcinoma (ccRCC), and demonstrated its proliferative role through positive feedback regulation of the phosphorylated form of signal transducer and activator of transcription 3. However, the role of G6PD in ccRCC invasion remains unclear. In the present study, reverse transcription-quantitative (RT-q) PCR, western blotting, enzyme activity assay, transwell assay and immunohistochemistry analysis in cell model, xenograft mice model and human specimen studies were performed to evaluate the role of G6PD in ccRCC invasion. The results from the present study demonstrated that G6PD may promote ccRCC cell invasive ability by increasing matrix metalloproteinase 2 (MMP2) mRNA and protein expression both in vitro and in vivo. In addition, a positive correlation between G6PD and MMP2 expression was demonstrated by RT-qPCR and western blotting in twenty pairs of ccRCC tumor specimens and matched adjacent normal tissues. Furthermore, G6PD promoted reactive oxygen species (ROS) generation and activated the MAPK signaling pathway in ccRCC cells. In addition, ROS significantly promoted the MAPK signaling pathway activation, which in turn contributed to MMP2 overexpression in ccRCC cells. In conclusion, the present study demonstrated that G6PD may facilitate ccRCC cell invasive ability by enhancing MMP2 expression through ROS-MAPK axis pathway.

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Section: Discussionmentioning

confidence: 99%

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

et al. 2020

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“…They also found that RAB31 may be as ERCC6L downstream protein involved in the progression of cancer via phosphorylated MAPK and CDK. Zhang et al [25] analyzed a tissue microarray containing 150 renal cell carcinoma (RCC) samples showed that compared with adjacent tissue, ERCC6L was overexpressed in the tumor tissues, and abnormal expression was positively correlated with the cancers progression. Meanwhile, knockdown ERCC6L expression inhibited RCC cells viability and induced apoptosis accordingly.…”

Section: Discussionmentioning

confidence: 99%

ERCC6L promotes the progression of hepatocellular carcinoma through activating PI3K/AKT and NF-κB signaling pathway

Han

Wang

et al. 2020

BMC Cancer

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Background: Excision Repair Cross-Complementation group 6-like (ERCC6L) has been shown to exhibit carcinogenic effect in several malignant tumors. However, the function and molecular mechanism of the ERCC6L in hepatocellular carcinoma (HCC) have not been investigated extensively. Methods: Immunohistochemistry analyses were used to detect ERCC6L expression in a HCC tissue microarray, and the Chi-square test was used to assess the correlation between ERCC6L expression and patients' clinicopathological features. shRNA was used to down-regulation ERCC6L expression in HCC cell lines. MTT assay, plate clone formation assay, flow cytometry, caspase 3/7 activity and migration assays were performed to evaluate the impact of ERCC6L on HCC cells in vitro. Nude mice xenograft models were used to assess the role of ERCC6L in vivo. The regulatory of mechanism of PI3K/AKT pathway was evaluated by western blotting. Results: ERCC6L was highly expressed in HCC tissue compared with tumor adjacent tissues in 90 paired samples. ERCC6L expression positively correlated with gender, tumor encapsulation, and pathological stage. Patients with low ERCC6L expression had significantly longer OS than those with high ERCC6L expression. Knockdown of ERCC6L expression significantly inhibited proliferation, invasion and metastasis in vitro and tumor growth in vivo, and it promoted cell cycle arrest and apoptosis. Mechanistic analyses revealed that PI3K/AKT and NF-κB signaling pathway were inhibited by silencing ERCC6L. Conclusion: These results demonstrate that ERCC6L plays a critical role in HCC progression, and thereby might be a potential therapeutic target for HCC patients.

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“…It was a mitotic target and substrate of polo-like kinases (PLKs) which regulates multiple processes in mammalian cell mitosis [28]. Downregulation of ERCC6L decreased cell viability in RCC cell lines by blocking mitogen-activated protein kinase (MAPK) signaling pathway and interactions with protein PLK1 [29]. Protein encoded by GTSE-1 modulated cell migrations in an EB1-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Identification of biomarkers of chromophobe renal cell carcinoma by weighted gene co-expression network analysis

2018

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BackgroundChromophobe renal cell carcinoma (ChRCC) is the second common subtype of non-clear cell renal cell carcinoma (nccRCC), which accounting for 4–5% of renal cell carcinoma (RCC). However, there is no effective bio-marker to predict clinical outcomes of this malignant disease. Bioinformatic methods may provide a feasible potential to solve this problem.MethodsIn this study, differentially expressed genes (DEGs) of ChRCC samples on The Cancer Genome Atlas database were filtered out to construct co-expression modules by weighted gene co-expression network analysis and the key module were identified by calculating module-trait correlations. Functional analysis was performed on the key module and candidate hub genes were screened out by co-expression and MCODE analysis. Afterwards, real hub genes were filter out in an independent dataset GSE15641 and validated by survival analysis.ResultsOverall 2215 DEGs were screened out to construct eight co-expression modules. Brown module was identified as the key module for the highest correlations with pathologic stage, neoplasm status and survival status. 29 candidate hub genes were identified. GO and KEGG analysis demonstrated most candidate genes were enriched in mitotic cell cycle. Three real hub genes (SKA1, ERCC6L, GTSE-1) were selected out after mapping candidate genes to GSE15641 and two of them (SKA1, ERCC6L) were significantly related to overall survivals of ChRCC patients.ConclusionsIn summary, our findings identified molecular markers correlated with progression and prognosis of ChRCC, which might provide new implications for improving risk evaluation, therapeutic intervention, and prognosis prediction in ChRCC patients.Electronic supplementary materialThe online version of this article (10.1186/s12935-018-0703-z) contains supplementary material, which is available to authorized users.

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ERCC6L that is up-regulated in high grade of renal cell carcinoma enhances cell viability in vitro and promotes tumor growth in vivo potentially through modulating MAPK signalling pathway

Cited by 19 publications

References 34 publications

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

G6PD facilitates clear cell renal cell carcinoma invasion by enhancing MMP2 expression through ROS‑MAPK axis pathway

ERCC6L promotes the progression of hepatocellular carcinoma through activating PI3K/AKT and NF-κB signaling pathway

Identification of biomarkers of chromophobe renal cell carcinoma by weighted gene co-expression network analysis

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