Gankyrin promotes breast cancer cell metastasis by regulating Rac1 activity

Zhen, Cheng; Chen, L; Zhao, Qing; Liu, Bing; Yx, Gu; Zf, Bai; Wang, K; Xu, Xiaowei; Qy, Han; Df, Fang; Sx, Wang; Zhou, Tao; Xia, Qing; Wl, Gong; Wang, N; Hy, Li; Bf, Jin; Jh, Man

doi:10.1038/onc.2012.356

Cited by 53 publications

(50 citation statements)

References 38 publications

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“…We previously reported that Gankyrin is overexpressed in human lung and breast cancers and plays an essential role in breast cancer metastasis (10,16). To determine the role of Gankyrin in tumor metastasis, we extended our observation to CRC given that Gankyrin promoted cell proliferation and tumor growth in a colon cancer cell line HCT116 as recently reported (33).…”

Section: Elevated Gankyrin Expression In Primary Colorectal Cancers Wmentioning

confidence: 99%

“…The siRNAs of Gankyrin and control Photinus pyralis luciferase gene were from Invitrogen, and the target sequences were described previously (10). The Lipofectamine reagent (Invitrogen) was used for transfections, and the final concentration of siRNA was 50 nmol/L.…”

Section: Cell Transfection and Transductionmentioning

confidence: 99%

“…Cell migration assays were carried out as previously described (10). Each determination represents the average of 3 individual experiments.…”

Section: Cell Migration and 3-dimensional Invasion Assaysmentioning

confidence: 99%

“…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%

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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: Elevated Gankyrin Expression In Primary Colorectal Cancers Wmentioning

confidence: 99%

Section: Cell Transfection and Transductionmentioning

confidence: 99%

“…Cell migration assays were carried out as previously described (10). Each determination represents the average of 3 individual experiments.…”

Section: Cell Migration and 3-dimensional Invasion Assaysmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Bai

Tai

et al. 2013

Cancer Research

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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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Small‐Molecule Inhibitors of the Proteasome's Regulatory Particle

2019

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Cells need to synthesize and degrade proteins consistently. Maintaining a balanced level of protein in the cell requires a carefully controlled system and significant energy. Degradation of unwanted or damaged proteins into smaller peptide units can be accomplished by the proteasome. The proteasome is composed of two main subunits. The first is the core particle (20S CP), and within this core particle are three types of threonine proteases. The second is the regulatory complex (19S RP), which has a myriad of activities including recognizing proteins marked for degradation and shuttling the protein into the 20S CP to be degraded. Small‐molecule inhibitors of the 20S CP have been developed and are exceptional treatments for multiple myeloma (MM). 20S CP inhibitors disrupt the protein balance, leading to cellular stress and eventually to cell death. Unfortunately, the 20S CP inhibitors currently available have dose‐limiting off‐target effects and resistance can be acquired rapidly. Herein, we discuss small molecules that have been discovered to interact with the 19S RP subunit or with a protein closely associated with 19S RP activity. These molecules still elicit their toxicity by preventing the proteasome from degrading proteins, but do so through different mechanisms of action.

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Gankyrin promotes breast cancer cell metastasis by regulating Rac1 activity

Cited by 53 publications

References 38 publications

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

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

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

Small‐Molecule Inhibitors of the Proteasome's Regulatory Particle

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