Wuli Zhao

Peking Union Medical College Hospital, Peping, Beijing, China

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Publications (8)19.58 Total impact

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    ABSTRACT: Myofibrillogenesis regulator-1 (MR-1) has been characterized as a tumor promoter in many cancers. However, its mechanism of action has not been fully elucidated. Here, we report that MR-1 is overexpressed in human breast cancer cells and participates in tumor promotion in human breast cancer MCF7 cells by activating the ERK1/2 signaling pathway. MR-1 interacts with MEK1/2 and ERK1, and its N-terminal sequence plays a major role in promoting the MEK/ERK cascade. Furthermore, six phosphorylation sites of MR-1 were identified, and phosphorylation at S46 was shown to be critical for the activation of MEK/ERK. Therefore, our findings suggest that MR-1 functions as a tumor promoter in MCF7 cells by activating the MEK/ERK signaling.
    FEBS letters. 07/2014;
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    ABSTRACT: Myofibrillogenesis regulator-1 (MR-1) is a gene overexpressed usually in many human cancers. However, the effects of MR-1 on cell proliferation, adhesion, migration and genome-wide gene regulation are still unclear. In this study, a human hepatoma cell line that highly overexpresses MR-1, BEL-7402/MR-1 cells was established. While the high expression of MR-1 did not promote cell proliferation, it significantly increased cell spreading, adhesion and migration compared with control cells. A total of 147 genes were regulated by MR-1 expression, 46 genes were down-regulated and 101 genes were up-regulated by MR-1 overexpression. Many of these genes were related to cell adhesion, cytoskeletal regulation, MAPK signaling, and cell cycle related pathways. Western blot analysis further confirmed the regulation of pathways associated with migration by MR-1. These results suggest that MR-1 is involved in the regulation of cancer cell adhesion, migration and related gene expression.
    Chinese Science Bulletin 08/2013; · 1.37 Impact Factor
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    ABSTRACT: Recently, tumor initiating cells are considered as the central role of tumorigenicity in hepatocellular carcinoma. Enediyne anticancer antibiotic lidamycin with great potential antitumor activity is currently evaluated in Phase II clinical trials. In this study, we evaluated the effect of lidamycin on tumor initiating cells of hepatocellular carcinoma Huh7 and identified the potential mechanism. Flow cytometry analysis and sorting assay, surface marker assay, sphere formation assay, and aldefluor assay were used to evaluate the effect of lidamycin on Huh7 tumor initiating cells in vitro. To investigate the potential mechanism, the activity of GSK3β/β-catenin pathway was detected by Western blot and T cell factors transcriptional activity assay. Subcutaneous tumor model in nude mice was used to observe in vivo effect of lidamycin on Huh7 cells. Lidamycin decreased the proportion of EpCAM(+) cells and the expression of EpCAM protein. Lidamycin inhibited sphere formation of sorted EpCAM(+) cells in 7 d, and of parental cells in three serial passages. The population of aldehyde dehydrogenase-positive cells was reduced by lidamycin. In addition, lidamycin restrained tumor volume and incidence in vivo. Lidamycin activated GSK3β, and degraded the activity of β-catenin. Consequently, transcriptional activity of β-catenin/T cell factors was decreased. In brief, these results suggest that lidamycin suppressed Huh7 tumor initiating cells via GSK3β/β-catenin pathway. These findings reveal the potential mechanism of lidamycin on tumor initiating cells and the benefit for further clinical evaluation. © 2013 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 07/2013; · 4.27 Impact Factor
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    ABSTRACT: The treatment of hepatocellular carcinoma (HCC) remains a challenge and the future of cancer therapy will incorporate rational combinations directed to molecular targets that cooperate to drive critical pro-survival signaling. Sphingosine kinase 1 (SphK1) has been shown to regulate various processes important for cancer progression. Given the up-regulated expression of SphK1 in response to the silence of N-ras and other interactions between Ras/ERK and SphK1, it was speculated that combined inhibition of Ras/ERK and SphK1 would create enhanced antitumor effects. Experimental results showed that dual blockage of N-ras/ERK and SphK1 resulted in enhanced growth inhibitions in human hepatoma cells. Similarly, MEK1/2 Inhibitor U0126 potentiated SKI II-induced apoptosis in hepatoma HepG2 cells, consistently with the further attenuation of Akt /ERK/NF-κB signaling pathway. It was also shown that the combination of SKI II and U0126 further attenuated the migration of hepatoma HepG2 cells via FAK/MLC-2 signaling pathway. Taken together, the dual inhibition of SphK1 and Ras/ERK pathway resulted in enhanced effects, which might be an effective therapeutic approach for the treatment of HCC.
    Biochemical and Biophysical Research Communications 03/2013; · 2.28 Impact Factor
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    ABSTRACT: Salmonella typhimurium is probably most extensively studied tumor-targeting bacteria and SL7207 is one of its attenuated strains. SL7207 was first made for bacterial vaccine development and its therapeutic efficacy and safety for hepatocellular carcinoma has not been characterized. In this study, the inhibitory ability of SL7207-lux on human hepatoma HepG2 cells was tested in vitro and in vivo. A bacterial luminescent gene cluster (lux CDABE) was transfected into SL7207 to better monitor the invasion of the bacteria. The results show that SL7207-lux can rapidly enter HepG2 cells and localize in the cytoplasm. This invasion represses cell proliferation and induces apoptosis. In vivo real-time invasion studies showed that the bacteria gradually accumulate in the tumor. This enrichment was confirmed by anatomic observation at 5 days after inoculation. About 40% of tumor growth was inhibited by SL7207-lux at 34 days post-treatment without significant loss of body weight. The area of necrosis of tumor tissue was clearly increased in the treated group. Bacterial quantification showed that the number of colony-forming units per gram of bacteria within tumor tissue was approximately 1000-fold higher than that of liver and spleen. These data suggest that attenuated S. typhimurium strain SL7207 has potential for the treatment of cancers.
    Acta Pharmaceutica Sinica B. 12/2012; 2(6):562–568.
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    ABSTRACT: Ras-GTPase-activating protein SH3 domain-binding proteins (G3BP) are overexpressed in various human tumors and participate in several signaling pathways involved in growth, differentiation and apoptosis. G3BP interact with RasGAP (Ras-GTPase activating protein) only in growing cells and depend on Ras activation, and participate in the Ras signal pathway. Therefore, the blockage and downregulation of G3BP may be a new strategy for cancer therapy. In this report, we demonstrate that a novel peptide GAP161 blocked the functions of G3BP and markedly suppressed HCT116 cell growth through the induction of apoptosis. The peptide bound with G3BP, which interfered with the interaction of G3BP1 with RasGAP and further suppressed Ras signaling pathways. GAP161 downregulated G3BP1 and G3BP2 proteins. Similarly, the knockdown of G3BP substantially decreased the proliferation of HCT116 cells and inhibited Ras signal pathways. Furthermore, the downregulation of G3BP could enhance cisplatin-induced apoptosis and growth inhibition of HCT116 cells. We also found that GAP161 suppressed the growth of BALB/c mice bearing colon CT26 tumors and nude mice bearing HCT116 xenografts. These results suggest that downregulation of G3BP might be useful in cancer therapy and that GAP161 is a promising new therapeutic agent for cancers. (Cancer Sci, doi: 10.1111/j.1349-7006.2012.02361.x, 2012).
    Cancer Science 06/2012; 103(10):1848-56. · 3.48 Impact Factor
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    ABSTRACT: EpCAM or CD133 has been used as the tumor initiating cells (TICs) marker in hepatocellular carcinoma (HCC). We investigated whether cells expressing with both EpCAM and CD133 surface marker were more representative for TICs in hepatocellular carcinoma Huh7 cells. Four different phenotypes of CD133(+)EpCAM(+), CD133(+)EpCAM(-), CD133(-)EpCAM(+) and CD133(-)EpCAM(-) in Huh7 cells were sorted by flow cytometry. Then cell differentiation, self-renewal, drug-resistance, spheroid formation and the levels of stem cell-related genes were detected to compare the characteristics of TICs. The ability of tumorigenicity was measured in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice to verify TICs. CD133(+)EpCAM(+) cells have many characteristics of TICs in Huh7 cells compared with CD133(+)EpCAM(-), CD133(-)EpCAM(+), CD133(-)EpCAM(-) cells, including enrichment in side population cells, higher differentiation capacity, increased colony-formation ability, preferential expression of stem cell-related genes, appearance of drug-resistant to some chemotherapeutics, more spheroid formation of culture cells and stronger tumorigenicity in NOD/SCID mice. CD133(+)EpCAM(+) phenotype is precisely represented TICs in Huh7 cells. It might be useful for studying biology mechanism of TICs in hepatocellular carcinoma and screening new targets for cancer therapy.
    International journal of biological sciences 01/2012; 8(7):992-1004. · 3.17 Impact Factor
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    ABSTRACT: To increase the efficacy of currently used anti-cancer genotoxins, a combination use of different drugs is a potential new therapeutical tool. Here, we reported that a synthetic RasGAP-derived peptide 38GAP with RasGAP(301-326) and TAT penetration sequences could enhance the effect of chemotherapeutic agent CDDP in human colon carcinoma HCT116 cells. Our results showed that 38GAP significantly increased the CDDP-induced apoptosis in HCT116 cells. This synergistic effect was associated with abrogation of CDDP-induced G2/M arrest by down-regulations of phospho-Cdc2 and p21, and inhibitions of phospho-AKT, phospho-ERK and NF-κB. In animal models, 38GAP combined with CDDP significantly suppressed CT26 tumor growth, while 38GAP alone showed slight inhibitory effect. Our data suggest that 38GAP in combination with chemotherapeutics will become a potential therapeutic strategy for colon cancers.
    Cancer letters 09/2011; 308(1):62-70. · 5.02 Impact Factor

Publication Stats

22 Citations
19.58 Total Impact Points


  • 2013–2014
    • Peking Union Medical College Hospital
      Peping, Beijing, China
    • Southwest University in Chongqing
      Pehpei, Chongqing Shi, China