Nature Communications (Jun 2016)
p62/Sqstm1 promotes malignancy of HCV-positive hepatocellular carcinoma through Nrf2-dependent metabolic reprogramming
- Tetsuya Saito,
- Yoshinobu Ichimura,
- Keiko Taguchi,
- Takafumi Suzuki,
- Tsunehiro Mizushima,
- Kenji Takagi,
- Yuki Hirose,
- Masayuki Nagahashi,
- Tetsuro Iso,
- Toshiaki Fukutomi,
- Maki Ohishi,
- Keiko Endo,
- Takefumi Uemura,
- Yasumasa Nishito,
- Shujiro Okuda,
- Miki Obata,
- Tsuguka Kouno,
- Riyo Imamura,
- Yukio Tada,
- Rika Obata,
- Daisuke Yasuda,
- Kyoko Takahashi,
- Tsutomu Fujimura,
- Jingbo Pi,
- Myung-Shik Lee,
- Takashi Ueno,
- Tomoyuki Ohe,
- Tadahiko Mashino,
- Toshifumi Wakai,
- Hirotatsu Kojima,
- Takayoshi Okabe,
- Tetsuo Nagano,
- Hozumi Motohashi,
- Satoshi Waguri,
- Tomoyoshi Soga,
- Masayuki Yamamoto,
- Keiji Tanaka,
- Masaaki Komatsu
Affiliations
- Tetsuya Saito
- Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences
- Yoshinobu Ichimura
- Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences
- Keiko Taguchi
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine
- Takafumi Suzuki
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine
- Tsunehiro Mizushima
- Department of Life Science, Picobiology Institute, Graduate School of Life Science, University of Hyogo, 3-2-1, Hyogo 678-1297, Japan
- Kenji Takagi
- Department of Life Science, Picobiology Institute, Graduate School of Life Science, University of Hyogo, 3-2-1, Hyogo 678-1297, Japan
- Yuki Hirose
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences
- Masayuki Nagahashi
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences
- Tetsuro Iso
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine
- Toshiaki Fukutomi
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine
- Maki Ohishi
- Institute for Advanced Biosciences, Keio University
- Keiko Endo
- Institute for Advanced Biosciences, Keio University
- Takefumi Uemura
- Department of Anatomy and Histology, Fukushima Medical University School of Medicine
- Yasumasa Nishito
- Core Technology and Research Center, Tokyo Metropolitan Institute of Medical Science
- Shujiro Okuda
- Bioinformatics Laboratory, Niigata University Graduate School of Medical and Dental Sciences
- Miki Obata
- Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences
- Tsuguka Kouno
- Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences
- Riyo Imamura
- The University of Tokyo, Drug Discovery Initiative, University of Tokyo
- Yukio Tada
- The University of Tokyo, Drug Discovery Initiative, University of Tokyo
- Rika Obata
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University
- Daisuke Yasuda
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University
- Kyoko Takahashi
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University
- Tsutomu Fujimura
- Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine
- Jingbo Pi
- Institute for Chemical Safety Sciences, Hamner Institutes for Health Sciences, Research Triangle Park
- Myung-Shik Lee
- Severance Biomedical Science Institute and Department of Internal Medicine, Yonsei University College of Medicine
- Takashi Ueno
- Laboratory of Proteomics and Biomolecular Science, Research Support Center, Juntendo University Graduate School of Medicine
- Tomoyuki Ohe
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University
- Tadahiko Mashino
- Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University
- Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences
- Hirotatsu Kojima
- The University of Tokyo, Drug Discovery Initiative, University of Tokyo
- Takayoshi Okabe
- The University of Tokyo, Drug Discovery Initiative, University of Tokyo
- Tetsuo Nagano
- The University of Tokyo, Drug Discovery Initiative, University of Tokyo
- Hozumi Motohashi
- Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University
- Satoshi Waguri
- Department of Anatomy and Histology, Fukushima Medical University School of Medicine
- Tomoyoshi Soga
- Institute for Advanced Biosciences, Keio University
- Masayuki Yamamoto
- Department of Medical Biochemistry, Tohoku University Graduate School of Medicine
- Keiji Tanaka
- Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science
- Masaaki Komatsu
- Department of Biochemistry, Niigata University Graduate School of Medical and Dental Sciences
- DOI
- https://doi.org/10.1038/ncomms12030
- Journal volume & issue
-
Vol. 7,
no. 1
pp. 1 – 16
Abstract
Dysregulation of p62 has been implicated in tumorigenesis. Here, the authors show that p62 promotes hepatocellular carcinoma by reprogramming glucose and glutamine metabolism through Nrf2 and present a novel compound that can inhibit p62 action thus sensitizing cancer cells to chemotherapy.
