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Your search keyword '"Gen Fujii"' showing total 2 results
2 results on '"Gen Fujii"'

1. Artesunate inhibits intestinal tumorigenesis through inhibiting wnt signaling

Author

Toshiyuki Sakai, Yosuke Iizumi, Tadashi Kondo, Kohei Miki, Jiro Toshima, Yui Matsuzawa, Takahiro Hamoya, Kenji Watanabe, Michihiro Mutoh, Takumi Narita, Masami Komiya, Gen Fujii, Keiji Wakabayashi, and Shinji Kishimoto

Subjects
Male, Transcriptional Activation, 0301 basic medicine, Cancer Research, Carcinogenesis, Adenomatous Polyposis Coli Protein, Drug Evaluation, Preclinical, Artesunate, Mice, Transgenic, medicine.disease_cause, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, In vivo, Cell Line, Tumor, T Cell Transcription Factor 1, medicine, Animals, Humans, Hepatocyte Nuclear Factor 1-alpha, Intestinal Mucosa, Nuclear protein, Promoter Regions, Genetic, Enhancer, Wnt Signaling Pathway, Cell Nucleus, Chemistry, Wnt signaling pathway, General Medicine, Gene Expression Regulation, Neoplastic, Disease Models, Animal, ran GTP-Binding Protein, 030104 developmental biology, Adenomatous Polyposis Coli, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Mutation, Ran, Cancer research, Signal transduction
Abstract

Artesunate (ART) is a clinically approved antimalarial drug and was revealed as a candidate of colorectal cancer chemopreventive agents in our drug screening system. Here, we aimed to understand the suppressive effects of ART on intestinal tumorigenesis. In vitro, ART reduced T-cell factor/lymphoid enhancer factor (TCF/LEF) promoter transcriptional activity. In vivo, ART inhibited intestinal polyp development. We found that ART reduces TCF1/TCF7 nuclear translocation by binding the Ras-related nuclear protein (RAN), suggesting that ART inhibits TCF/LEF transcriptional factor nuclear translocation by binding to RAN, thereby inhibiting Wnt signaling. Our results provide a novel mechanism through which artesunate inhibits intestinal tumorigenesis.

Published
2020

2. Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor-κB/mitogen-activated protein kinase

Author

Kosuke Tashiro, Mitsuteru Natsuizaka, Kanako C. Hatanaka, Hideki Yokoo, Mitsuru Nakanishi, Masahiro Asaka, Goki Suda, Makoto Chuma, Takuya Sho, Shuhei Hige, Gen Fujii, Naoya Sakamoto, Yoshihiro Matsuno, Mitsuaki Fujimoto, Akira Nakai, Toshiya Kamiyama, Akinobu Taketomi, Shin Maeda, and Yoko Hikiba

Subjects
Adult, Cancer Research, Carcinoma, Hepatocellular, Blotting, Western, Apoptosis, IκB kinase, Mice, SCID, Small hairpin RNA, Immunoenzyme Techniques, Mice, Heat Shock Transcription Factors, Animals, Humans, Heat shock, RNA, Small Interfering, Protein kinase A, HSF1, Cells, Cultured, Cell Proliferation, Chemistry, fungi, Liver Neoplasms, NF-kappa B, General Medicine, Heat shock factor, DNA-Binding Proteins, Mice, Inbred C57BL, Cell Transformation, Neoplastic, Cancer research, Hepatocytes, Tumor necrosis factor alpha, Signal transduction, Mitogen-Activated Protein Kinases, Transcription Factors
Abstract

Heat shock factor 1 (HSF1), a major transactivator of stress responses, has been implicated in carcinogenesis in various organs. However, little is known about the biological functions of HSF1 in the development of hepatocellular carcinoma (HCC). To clarify the functional role of HSF1 in HCC, we established HSF1-knockdown (HSF1 KD) KYN2 HCC cells by stably expressing either small hairpin RNA (shRNA) against HSF1 (i.e. HSF1 KD) or control shRNA (HSF1 control). Tumorigenicity was significantly reduced in orthotopic mice with HSF1 KD cells compared with those with HSF1 control cells. Reduced tumorigenesis in HSF1 KD cells appeared attributable to increased apoptosis and decreased proliferation. Tumor necrosis factor-α-induced apoptosis was increased in HSF1 KD cells and HSF1(-/-) mouse hepatocytes compared with controls. Decreased expression of IκB kinase γ, a positive regulator of nuclear factor-κB, was also observed in HSF1 KD cells and HSF1(-/-) mouse hepatocytes. Furthermore, expression of bcl-2-associated athanogene domain 3 (BAG3) was dramatically reduced in HSF1 KD cells and HSF1(-/-) mouse hepatocytes. We also found that epidermal growth factor-stimulated mitogen-activated protein kinase signaling was impaired in HSF1 KD cells. Clinicopathological analysis demonstrated frequent overexpression of HSF1 in human HCCs. Significant correlations between HSF1 and BAG3 protein levels and prognosis were also observed. In summary, these results identify a mechanistic link between HSF1 and liver tumorigenesis and may provide as a potential molecular target for the development of anti-HCC therapies.

Published
2013

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