Gankyrin promotes tumor growth and metastasis through activation of IL-6/STAT3 signaling in human cholangiocarcinoma

Zheng, Tongsen; Hong, Xuehui; Wang, Jiabei; Pei, Tiemin; Liang, Yingjian; Yin, Dalong; Song, Ran; Song, Xuan; Lu, Zhao-Yang; Qi, Shuyi; Liu, Jiaren; Sun, Bei; Xie, Changming; Pan, Shangha; Li, Yuejin; Luo, Xu; Li, Shuai; Fang, Xiang; Bhatta, Nishant; Jiang, Hongchi; Liu, Lianxin

doi:10.1002/hep.26705

Cited by 91 publications

(70 citation statements)

References 36 publications

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“…Overexpression of Gankyrin in cells increases the ratio of polyubiquitinated versus monoubiquitinated p53. Overexpression of Gankyrin is reported in hepatocellular carcinoma, colorectal cancer, pancreatic cancer, esophageal squamous cell carcinoma, and breast cancer (Zheng et al 2014). Gankyrin is located on the X chromosome and has not been deleted in model systems to analyze its functions.…”

Section: Mefs Derived From Ube4bmentioning

confidence: 99%

Limiting the power of p53 through the ubiquitin proteasome pathway

2014

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The ubiquitin proteasome pathway is critical in restraining the activities of the p53 tumor suppressor. Numerous E3 and E4 ligases regulate p53 levels. Additionally, deubquitinating enzymes that modify p53 directly or indirectly also impact p53 function. When alterations of these proteins result in increased p53 activity, cells arrest in the cell cycle, senesce, or apoptose. On the other hand, alterations that result in decreased p53 levels yield tumor-prone phenotypes. This review focuses on the physiological relevance of these important regulators of p53 and their therapeutic implications.

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Section: Mefs Derived From Ube4bmentioning

confidence: 99%

Limiting the power of p53 through the ubiquitin proteasome pathway

2014

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“…Gankyrin is a chaperone of the ubiquitin-proteasome and a novel oncogene, and has been demonstrated to be overexpressed in numerous types of cancer (25)(26)(27), including liver cancer (28)(29)(30), breast cancer (31,32), colorectal cancer (33), estrogen-driven endometrial carcinoma (26) and oral cancer (34). Gankyrin serves an essential role in tumor occurrence and development (25)(26)(27)(28)(29)(30)(31)(32)(33)(34). p115 is a tether protein that has an important role in a number of signaling pathways required for cell proliferation, and has been extensively studied (35,36).…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

Wang

Chen

et al. 2017

Oncology Letters

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Abstract.The transforming growth factor-β (TGF-β) signaling pathway serves a key role in the pathogenesis of liver cancer. To investigate the association between TGF-β1 and the following proteins: Proliferating cell nuclear antigen (PCNA), gankyrin, general vesicular transport factor p115 (p115), X-linked inhibitor of apoptosis protein (XIAP) and survivin, HepG2 liver cancer cells were transfected with small interfering RNA (siRNA) directed against TGF-β1, or were treated with exogenous TGF-β1. TGF-β1 protein expression levels were assessed at 72 and 96 h using western blotting, cell growth was evaluated using a Cell Counting kit-8 assay, and flow cytometry was used to examine cell cycle distribution and apoptosis. In addition, PCNA, gankyrin, p115, XIAP and survivin protein levels were evaluated using western blotting. TGF-β1 protein expression levels were decreased at 72 and 96 h following siRNA transfection, indicating that the siRNA against TGF-β1 was effective. In the TGF-β1-knockdown group, the HepG2 cells exhibited G 1 or S-phase cell cycle arrest; therefore, the number of G 2 -phase cells was decreased, cell growth was inhibited and apoptotic peaks were observed. By contrast, no significant alteration in cell cycle distribution or apoptosis was observed in the cells treated with exogenous TGF-β1. In the exogenous TGF-β1 group, PCNA and XIAP protein expression levels were increased, whereas gankyrin, p115 and survivin protein expression was observed to be dependent on the duration of treatment. By contrast, PCNA, gankyrin, XIAP and survivin protein expression decreased following TGF-β1 knockdown; however, p115 protein expression increased. In conclusion, the TGF-β1 signaling pathway may affect cell growth, cell cycle distribution and apoptosis through the regulation of PCNA, gankyrin, p115, XIAP and survivin protein expression in liver cancer. The results of the present study may improve the current understanding of the role of the TGF-β signaling pathway during the pathogenesis of liver cancer.

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“…Gankyrin was initially purified and characterized by Tanaka and coworkers as the p28 component of the regulatory subunit of the 26S proteasome, which is an ATP-dependent protease responsible for the degradation of proteins [17]. Ectopically expressed gankyrin was shown to bind retinoblastoma protein (Rb), but not the pRb-related proteins p107 and p130 in vitro and in vivo, providing an initial glimpse into the role of gankyrin in tumorigenesis [18]. Overexpression of gankyrin also conferred tumorigenicity to NIH/3T3 cells and inhibited apoptosis in cultured human tumor cells exposed to chemotherapeutic agents [19].…”

Section: Introductionmentioning

confidence: 99%

Association Between Functional PSMD10 Rs111638916 Variant Regulated by MiR-505 and Gastric Cancer Risk in a Chinese Population

Liu

Jiang

et al. 2015

Cell Physiol Biochem

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Background/Aims: Gankyrin is an oncoprotein involved in regulating the cell cycle through protein-protein interactions with cyclin-dependent kinase 4 and p53. However, its association with gastric cancer (GC) risk has not yet been determined. In this study, we investigated micro RNA (miRNA)-associated single nucleotide polymorphisms (SNPs) in the 3′-untranslated region (UTR) of the gankyrin gene PSMD10 to clarify the relationship between these SNPs and miRNAs in Chinese patients with GC. Methods: We performed a case-control study including 857 GC patients and 748 cancer-free controls. PSMD10 expression was investigated using genotyping, real-time polymerase chain reaction, cell transfection, and dual luciferase reporter assays. Results: Patients with histories of smoking, alcohol consumption, and cancer were more susceptible to GC than controls. The SNP rs111638916 in the PSMD10 3′-UTR was identified as a risk factor for GC and acted as a tumor promoting factor. SNP rs111638916 was also regulated by miR-505, resulting in up-regulation of gankyrin expression in patients with GA and AA genotypes. Carriers of the GA and AA genotypes also presented with larger tumors and had a higher risk of metastasis. Conclusion: The PSMD10 rs111638916 SNP is highly associated with an increased risk of GC in Chinese patients, and could serve as a novel biomarker for this disease.

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Gankyrin promotes tumor growth and metastasis through activation of IL-6/STAT3 signaling in human cholangiocarcinoma

Cited by 91 publications

References 36 publications

Limiting the power of p53 through the ubiquitin proteasome pathway

Limiting the power of p53 through the ubiquitin proteasome pathway

TGF-β1 signaling pathway serves a role in HepG2 cell regulation by affecting the protein expression of PCNA, gankyrin, p115, XIAP and survivin

Association Between Functional PSMD10 Rs111638916 Variant Regulated by MiR-505 and Gastric Cancer Risk in a Chinese Population

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