Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer

Tang, Shanhong; Yang, Guitao; Meng, Yanlong; Du, Rui; Li, Xiaohua; Fan, Rui; Zhao, Lina; Bi, Qian; Jin, Jianhua; Gao, Liucun; Zhang, Lin; Li, Hao; Fan, Meng; Wang, Yingmei; Wu, Kaijie; Liu, Jie; Fan, Daiming

doi:10.4161/cbt.9.2.10283

Cited by 48 publications

(46 citation statements)

References 25 publications

(27 reference statements)

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“…The expression of Gankyrin has been investigated in a variety of cancers with nearly universal findings that showed elevated protein and/or mRNA levels in cancers when compared with normal counterparts (4)(5). Gankyrin has been shown to be involved in carcinogenesis and oncogene-induced tumor onset and progression (4,(6)(7)(8)(9)(10). Overexpression of Gankyrin promotes cellular proliferation by targeting retinoblastoma protein (Rb), leading to subsequent Rb degradation, activation of E2F transcription factor, and DNA synthesis of genes required for G 1 -S-phase transition (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Bai

Tai

et al. 2013

Cancer Research

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Hepatic metastasis is responsible for the majority of colorectal cancer (CRC)-related mortalities. Although Gankyrin (PSMD10) has been implicated in cancer metastasis, its exact role and underlying mechanisms of CRC hepatic metastasis remain largely unknown. Herein, we showed that the expression of Gankyrin was higher in primary CRC with hepatic metastasis compared with CRC without metastasis. RNAi-mediated silencing of Gankyrin expression in highly metastatic human CRC cells impaired their migratory and metastatic capacity in vivo. Genome-wide transcriptome profiling revealed activation of the interleukin (IL)-8 signaling pathway by Gankyrin. Protein levels of IL-8 and cyclin D1 (CCND1), the two important molecules in the IL-8 pathway, were positively correlated with Gankyrin expression in human CRC specimens. Furthermore, genetic deletion of cyclin D1 showed its requirement in Gankyrin-mediated cell migration. Finally, administration of recombinant IL-8 rescued the migratory defect of CRC cells where Gankyrin expression was silenced. Together, our findings highlight the importance of Gankyrin in hepatic metastasis of CRC and point out its candidature as a potential prognostic marker and therapeutic target to improve the clinical management of metastatic CRC. Cancer Res; 73(14); 4548-58. Ó2013 AACR.

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Section: Introductionmentioning

confidence: 99%

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Bai

Tai

et al. 2013

Cancer Research

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“…Examination of gankyrin expression in colorectral carcinoma (CRC) samples showed that gankyrin is dramatically increased in majority of CRC samples [72]. It has been shown that RNAi-mediated inhibition of gankyrin in the CRC cells inhibits proliferation of these cells [72].…”

Section: Introductionmentioning

confidence: 99%

Intracellular signaling and hepatocellular carcinoma

Iakova

Timchenko²,

Timchenko³

2011

Seminars in Cancer Biology

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Liver cancer is the fifth most common cancer and the third most common cause of cancer related death in the world. The recent development of new techniques for the investigations of global change in the gene expression, signaling pathways and wide genome binding has provided novel information for the mechanisms underlying liver cancer progression. Although these studies identified gene expression signatures in hepatocelluar carcinoma, the early steps of the development of hepatocellular carcinomas (HCC) are not well understood. The development of HCC is a multistep process which includes the progressive alterations of gene expression leading to the increased proliferation and to liver cancer. This review summarizes recent progress in the identification of the key steps of the development of HCC with the focus on early events of carcinogenesis and on the role of translational and epigenetic alterations in the development of HCC. Quiescent stage of the liver is supported by several tumor suppressor proteins including p53, Rb and C/EBPα. Studies with chemical models of liver carcinogenesis and with human HCC have shown that the elevation of gankyrin is responsible for the elimination of these three proteins at early steps of carcinogenesis. Later stages of progression of the liver cancer are associated with alterations in many signaling pathways including translation which leads to epigenetic silencing/activation of many genes. Particularly, recent reports suggest a critical role of histone deacetylase 1, HDAC1, in the development of HCC through the interactions with transcription factors such as C/EBP family proteins.

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“…6 In addition, gankyrin plays an essential role in Ras-initiated tumorigenesis, which is operative in ∼30% of all cancers. 7 Protein–protein interactions (PPIs) involving gankyrin are of great interest in basic research and as therapeutic targets.…”

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confidence: 99%

Characterization of the Binding Interaction between the Oncoprotein Gankyrin and a Grafted S6 ATPase

2014

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A complex with the C-terminal portion of the proteosomal subunit S6 ATPase is the only available structure of a protein–protein interaction involving the oncoprotein gankyrin. However, difficulties associated with recombinant expression of S6 ATPase alone, or truncations thereof, have limited our understanding of this assembly. We replaced the C-terminal portion of FtsH from Escherichia coli with the structurally homologous C-terminal portion of S6 ATPase and used this grafted protein to characterize the gankyrin–S6 ATPase binding interaction by isothermal titration calorimetry.

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Overexpression of a novel gene gankyrin correlates with the malignant phenotype of colorectal cancer

Cited by 48 publications

References 25 publications

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Gankyrin Activates IL-8 to Promote Hepatic Metastasis of Colorectal Cancer

Intracellular signaling and hepatocellular carcinoma

Characterization of the Binding Interaction between the Oncoprotein Gankyrin and a Grafted S6 ATPase

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