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3. SETD2 regulates SLC family transporter-mediated sodium and glucose reabsorptions in renal tubule

Author

Mitome, Taku, primary, Wakui, Hiromichi, additional, Azushima, Kengo, additional, Uehara, Tatsuki, additional, Jikuya, Ryosuke, additional, Ohtake, Shinji, additional, Noguchi, Go, additional, Kawaura, Sachi, additional, Iribe, Yasuhiro, additional, Aomori, Kota, additional, Tatenuma, Tomoyuki, additional, Ito, Hiroki, additional, Kawahara, Takashi, additional, Komeya, Mitsuru, additional, Ito, Yusuke, additional, Muraoka, Kentaro, additional, Furuya, Mitsuko, additional, Kato, Ikuma, additional, Fujii, Satoshi, additional, Nagahama, Kiyotaka, additional, Nishiyama, Akira, additional, Tamura, Tomohiko, additional, Kimura, Yayoi, additional, Kawagoe, Tatsukata, additional, Mizuki, Nobuhisa, additional, Huang, Gang, additional, Uemura, Hiroji, additional, Yao, Masahiro, additional, Makiyama, Kazuhide, additional, Tamura, Kouichi, additional, and Hasumi, Hisashi, additional

Published
2024
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4. Single-cell transcriptomes underscore genetically distinct tumor characteristics and microenvironment for hereditary kidney cancers

Author

Jikuya, Ryosuke, Murakami, Koichi, Nishiyama, Akira, Kato, Ikuma, Furuya, Mitsuko, Nakabayashi, Jun, Ramilowski, Jordan A., Hamanoue, Haruka, Maejima, Kazuhiro, Fujita, Masashi, Mitome, Taku, Ohtake, Shinji, Noguchi, Go, Kawaura, Sachi, Odaka, Hisakazu, Kawahara, Takashi, Komeya, Mitsuru, Shinoki, Risa, Ueno, Daiki, Ito, Hiroki, Ito, Yusuke, Muraoka, Kentaro, Hayashi, Narihiko, Kondo, Keiichi, Nakaigawa, Noboru, Hatano, Koji, Baba, Masaya, Suda, Toshio, Kodama, Tatsuhiko, Fujii, Satoshi, Makiyama, Kazuhide, Yao, Masahiro, Shuch, Brian M., Schmidt, Laura S., Linehan, W. Marston, Nakagawa, Hidewaki, Tamura, Tomohiko, and Hasumi, Hisashi

Published
2022
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6. Alternative magnetic field exposure suppresses tumor growth via metabolic reprogramming.

Author

Akimoto, Taisuke, Islam, Md Rafikul, Nagasako, Akane, Kishi, Kazuhito, Nakakaji, Rina, Ohtake, Makoto, Hasumi, Hisashi, Yamaguchi, Takashi, Yamada, Shigeki, Yamamoto, Tetsuya, Ishikawa, Yoshihiro, and Umemura, Masanari

Abstract

Application of physical forces, ranging from ultrasound to electric fields, is recommended in various clinical practice guidelines, including those for treating cancers and bone fractures. However, the mechanistic details of such treatments are often inadequately understood, primarily due to the absence of comprehensive study models. In this study, we demonstrate that an alternating magnetic field (AMF) inherently possesses a direct anti‐cancer effect by enhancing oxidative phosphorylation (OXPHOS) and thereby inducing metabolic reprogramming. We observed that the proliferation of human glioblastoma multiforme (GBM) cells (U87 and LN229) was inhibited upon exposure to AMF within a specific narrow frequency range, including around 227 kHz. In contrast, this exposure did not affect normal human astrocytes (NHA). Additionally, in mouse models implanted with human GBM cells in the brain, daily exposure to AMF for 30 min over 21 days significantly suppressed tumor growth and prolonged overall survival. This effect was associated with heightened reactive oxygen species (ROS) production and increased manganese superoxide dismutase (MnSOD) expression. The anti‐cancer efficacy of AMF was diminished by either a mitochondrial complex IV inhibitor or a ROS scavenger. Along with these observations, there was a decrease in the extracellular acidification rate (ECAR) and an increase in the oxygen consumption rate (OCR). This suggests that AMF‐induced metabolic reprogramming occurs in GBM cells but not in normal cells. Our results suggest that AMF exposure may offer a straightforward strategy to inhibit cancer cell growth by leveraging oxidative stress through metabolic reprogramming. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Enfortumab vedotin prolongs overall survival in metastatic urothelial carcinoma following pembrolizumab therapy in real‐world data.

Author

Uemura, Koichi, Ito, Hiroki, Jikuya, Ryosuke, Kondo, Takuya, Tatenuma, Tomoyuki, Kawahara, Takashi, Ito, Yusuke, Komeya, Mitsuru, Muraoka, Kentaro, Hasumi, Hisashi, Uemura, Hiroji, and Makiyama, Kazuhide

Subjects
TRANSITIONAL cell carcinoma, OVERALL survival, PEMBROLIZUMAB, ANTIBODY-drug conjugates, ELECTRIC vehicles
Abstract

Objective: In December 2021, enfortumab vedotin (EV), an antibody‐drug conjugate directed against nectin‐4, was approved in Japan as a new treatment after platinum‐containing chemotherapy and PD‐1/PD‐L1 inhibitors. This study evaluated, using real‐world data, the efficacy and safety of EV therapy in patients with metastatic urothelial carcinoma (mUC). Materials and methods: Fifty‐five patients with mUC who discontinued pembrolizumab therapy due to disease progression between June 2018 and April 2023 at Yokohama City University Hospital were evaluated retrospectively. Of the 55 patients, 25 received EV therapy (EV group) and 30 did not (non‐EV group). All patients who underwent EV therapy were diagnosed with disease progression after the approval of EV in Japan. Results: The median (range) follow‐up period after pembrolizumab discontinuation was 6.3 (0.7–31.1) months. There were eight (32.0%) deaths due to cancer in the EV group and 27 (90.0%) in the non‐EV group. The overall survival (OS) after pembrolizumab discontinuation was not reached in the EV group versus 2.6 months in the non‐EV group (p < 0.001). A multivariate analysis revealed that EV therapy (EV vs. non‐EV group; hazard ratio 0.26; 95% confidence interval 0.16–0.41; p < 0.001) was an independent prognostic factor for OS. Conclusion: EV prolonged OS in mUC following pembrolizumab therapy in real‐world data. [ABSTRACT FROM AUTHOR]

Published
2024
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8. Impacts of Complete Endophytic Renal Tumors on Surgical, Functional, and Oncological Outcomes of Robot-Assisted Partial Nephrectomy

Author

Ito, Hiroki, primary, Uemura, Koichi, additional, Ikeda, Maiko, additional, Jikuya, Ryosuke, additional, Kondo, Takuya, additional, Tatenuma, Tomoyuki, additional, Kawahara, Takashi, additional, Komeya, Mitsuru, additional, Ito, Yusuke, additional, Muraoka, Kentaro, additional, Hasumi, Hisashi, additional, and Makiyama, Kazuhide, additional

Published
2024
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9. Surgical proficiency in laparoscopic radical cystectomy with extracorporeal urinary diversion and its adequacy for the execution of robot‐assisted radical cystectomy with intracorporeal urinary diversion

Author

Suzuki, Atsuto, primary, Ito, Hiroki, additional, Uemura, Koichi, additional, Muraoka, Kentaro, additional, Tatenuma, Tomoyuki, additional, Osaka, Kimito, additional, Yokomizo, Yumiko, additional, Hayashi, Narihiko, additional, Hasumi, Hisashi, additional, and Makiyama, Kazuhide, additional

Published
2024
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15. Outcomes of treatment for localized prostate cancer in a single institution: comparison of radical prostatectomy and radiation therapy by propensity score matching analysis

Author

Hayashi, Narihiko, Osaka, Kimito, Muraoka, Kentaro, Hasumi, Hisashi, Makiyama, Kazuhide, Kondo, Keiichi, Nakaigawa, Noboru, Yao, Masahiro, Mukai, Yuki, Sugiura, Madoka, Takano, Shoko, Ito, Eiko, Kaizu, Hisashi, Koike, Izumi, Hata, Masaharu, Taguri, Masataka, Miyoshi, Yasuhide, Izumi, Koji, Kawahara, Takashi, and Uemura, Hiroji

Published
2020
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18. Predictive factors for pentafecta achievement in robot‐assisted partial nephrectomy for intermediate highly complex RENAL tumors (RENAL score ≥ 7).

Author

Uemura, Koichi, Ito, Hiroki, Ikeda, Maiko, Uehara, Koichiro, Tatenuma, Tomoyuki, Komeya, Mitsuru, Ito, Yusuke, Muraoka, Kentaro, Hasumi, Hisashi, and Makiyama, Kazuhide

Subjects
KIDNEY tumors, NEPHRECTOMY, SURGICAL robots, SURGICAL complications, POSTOPERATIVE period, LOGISTIC regression analysis
Abstract

Objectives: To investigate the predictive factors for pentafecta achievement of robot‐assisted partial nephrectomy (RAPN) for intermediate highly complex renal tumors (RENAL score ≥ 7). Methods: We retrospectively analyzed the data of 247 patients with renal tumors with a RENAL score ≥ 7 who underwent RAPN. Baseline characteristics and perioperative outcomes were compared between the pentafecta achieved group and the unachieved group. A multivariable logistic regression model was used to identify the predictive factors for pentafecta achievement for cT1 renal tumors with a RENAL score ≥ 7. Results: Of the 247 patients, 75 (30.3%) patients were in the achieved group and 172 (69.7%) patients were in the unachieved group. The median warm ischemia time and total operation time were 18 min versus 23 min (p < 0.001) and 179 min versus 201 min (p < 0.001) in the achieved and unachieved groups, respectively. In the unachieved group, six patients (3.4%) had major perioperative complications (Clavien–Dindo classification system ≥3). The median preservation rates of estimated GFR at the 1‐year postoperative period were 96.5% versus 83.0% (p < 0.001) in the achieved and unachieved groups. Multivariable logistic regression models revealed that age and tumor size were independent predictive factors for pentafecta achievement for cT1 renal tumors with a RENAL score ≥ 7. There were no significant differences in cancer‐free survival between the two groups (p = 0.456). Conclusion: Age and tumor size were independent predictive factors for pentafecta achievement, although there was no difference in oncological outcomes between the pentafecta achieved group and the unachieved group in RAPN for cT1 renal tumors with a RENAL score ≥ 7. [ABSTRACT FROM AUTHOR]

Published
2023
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19. Administration of Enfortumab Vedotin after Immune-Checkpoint Inhibitor and the Prognosis in Japanese Metastatic Urothelial Carcinoma: A Large Database Study on Enfortumab Vedotin in Metastatic Urothelial Carcinoma

Author

Kawahara, Takashi, primary, Hasizume, Akihito, additional, Uemura, Koichi, additional, Yamaguchi, Katsuya, additional, Ito, Hiroki, additional, Takeshima, Teppei, additional, Hasumi, Hisashi, additional, Teranishi, Jun-ichi, additional, Ousaka, Kimito, additional, Makiyama, Kazuhide, additional, and Uemura, Hiroji, additional

Published
2023
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20. Comparative analyses define differences between BHD-associated renal tumour and sporadic chromophobe renal cell carcinoma

Author

Jikuya, Ryosuke, primary, Johnson, Todd A., additional, Maejima, Kazuhiro, additional, An, Jisong, additional, Ju, Young-Seok, additional, Lee, Hwajin, additional, Ha, Kyungsik, additional, Song, WooJeung, additional, Kim, Youngwook, additional, Okawa, Yuki, additional, Sasagawa, Shota, additional, Kanazashi, Yuki, additional, Fujita, Masashi, additional, Imoto, Seiya, additional, Mitome, Taku, additional, Ohtake, Shinji, additional, Noguchi, Go, additional, Kawaura, Sachi, additional, Iribe, Yasuhiro, additional, Aomori, Kota, additional, Tatenuma, Tomoyuki, additional, Komeya, Mitsuru, additional, Ito, Hiroki, additional, Ito, Yusuke, additional, Muraoka, Kentaro, additional, Furuya, Mitsuko, additional, Kato, Ikuma, additional, Fujii, Satoshi, additional, Hamanoue, Haruka, additional, Tamura, Tomohiko, additional, Baba, Masaya, additional, Suda, Toshio, additional, Kodama, Tatsuhiko, additional, Makiyama, Kazuhide, additional, Yao, Masahiro, additional, Shuch, Brian M., additional, Ricketts, Christopher J., additional, Schmidt, Laura S., additional, Linehan, W. Marston, additional, Nakagawa, Hidewaki, additional, and Hasumi, Hisashi, additional

Published
2023
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21. Blood and lymphatic systems are segregated by the FLCN tumor suppressor

Author

Tai-Nagara, Ikue, Hasumi, Yukiko, Kusumoto, Dai, Hasumi, Hisashi, Okabe, Keisuke, Ando, Tomofumi, Matsuzaki, Fumio, Itoh, Fumiko, Saya, Hideyuki, Liu, Chang, Li, Wenling, Mukouyama, Yoh-suke, Marston Linehan, W., Liu, Xinyi, Hirashima, Masanori, Suzuki, Yutaka, Funasaki, Shintaro, Satou, Yorifumi, Furuya, Mitsuko, Baba, Masaya, and Kubota, Yoshiaki

Published
2020
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22. Molecular chaperone TRAP1 regulates a metabolic switch between mitochondrial respiration and aerobic glycolysis.

Author

Yoshida, Soichiro, Tsutsumi, Shinji, Muhlebach, Guillaume, Sourbier, Carole, Lee, Min-Jung, Lee, Sunmin, Vartholomaiou, Evangelia, Tatokoro, Manabu, Beebe, Kristin, Miyajima, Naoto, Mohney, Robert, Chen, Yang, Hasumi, Hisashi, Xu, Wanping, Fukushima, Hiroshi, Koga, Fumitaka, Kihara, Kazunori, Trepel, Jane, Picard, Didier, Neckers, Leonard, and Nakamura, Ken

Subjects
Animals, COS Cells, CSK Tyrosine-Protein Kinase, Chlorocebus aethiops, Glycolysis, HSP90 Heat-Shock Proteins, HeLa Cells, Humans, Intracellular Signaling Peptides and Proteins, Mice, Mice, Knockout, Mitochondria, Mitochondrial Proteins, Molecular Chaperones, NIH 3T3 Cells, Neoplasm Invasiveness, Oxidative Phosphorylation, RNA Interference, Transfection, src-Family Kinases
Abstract

TRAP1 (TNF receptor-associated protein), a member of the HSP90 chaperone family, is found predominantly in mitochondria. TRAP1 is broadly considered to be an anticancer molecular target. However, current inhibitors cannot distinguish between HSP90 and TRAP1, making their utility as probes of TRAP1-specific function questionable. Some cancers express less TRAP1 than do their normal tissue counterparts, suggesting that TRAP1 function in mitochondria of normal and transformed cells is more complex than previously appreciated. We have used TRAP1-null cells and transient TRAP1 silencing/overexpression to show that TRAP1 regulates a metabolic switch between oxidative phosphorylation and aerobic glycolysis in immortalized mouse fibroblasts and in human tumor cells. TRAP1-deficiency promotes an increase in mitochondrial respiration and fatty acid oxidation, and in cellular accumulation of tricarboxylic acid cycle intermediates, ATP and reactive oxygen species. At the same time, glucose metabolism is suppressed. TRAP1-deficient cells also display strikingly enhanced invasiveness. TRAP1 interaction with and regulation of mitochondrial c-Src provide a mechanistic basis for these phenotypes. Taken together with the observation that TRAP1 expression is inversely correlated with tumor grade in several cancers, these data suggest that, in some settings, this mitochondrial molecular chaperone may act as a tumor suppressor.

Published
2013

23. Data from TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease

Author

Baba, Masaya, primary, Furuya, Mitsuko, primary, Motoshima, Takanobu, primary, Lang, Martin, primary, Funasaki, Shintaro, primary, Ma, Wenjuan, primary, Sun, Hong-Wei, primary, Hasumi, Hisashi, primary, Huang, Ying, primary, Kato, Ikuma, primary, Kadomatsu, Tsuyoshi, primary, Satou, Yorifumi, primary, Morris, Nicole, primary, Karim, Baktiar O., primary, Ileva, Lilia, primary, Kalen, Joseph D., primary, Wilan Krisna, Luh Ade, primary, Hasumi, Yukiko, primary, Sugiyama, Aiko, primary, Kurahashi, Ryoma, primary, Nishimoto, Koshiro, primary, Oyama, Masafumi, primary, Nagashima, Yoji, primary, Kuroda, Naoto, primary, Araki, Kimi, primary, Eto, Masatoshi, primary, Yao, Masahiro, primary, Kamba, Tomomi, primary, Suda, Toshio, primary, Oike, Yuichi, primary, Schmidt, Laura S., primary, and Linehan, W. Marston, primary

Published
2023
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24. Supplemental Figure legends from TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease

Author

Baba, Masaya, primary, Furuya, Mitsuko, primary, Motoshima, Takanobu, primary, Lang, Martin, primary, Funasaki, Shintaro, primary, Ma, Wenjuan, primary, Sun, Hong-Wei, primary, Hasumi, Hisashi, primary, Huang, Ying, primary, Kato, Ikuma, primary, Kadomatsu, Tsuyoshi, primary, Satou, Yorifumi, primary, Morris, Nicole, primary, Karim, Baktiar O., primary, Ileva, Lilia, primary, Kalen, Joseph D., primary, Wilan Krisna, Luh Ade, primary, Hasumi, Yukiko, primary, Sugiyama, Aiko, primary, Kurahashi, Ryoma, primary, Nishimoto, Koshiro, primary, Oyama, Masafumi, primary, Nagashima, Yoji, primary, Kuroda, Naoto, primary, Araki, Kimi, primary, Eto, Masatoshi, primary, Yao, Masahiro, primary, Kamba, Tomomi, primary, Suda, Toshio, primary, Oike, Yuichi, primary, Schmidt, Laura S., primary, and Linehan, W. Marston, primary

Published
2023
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25. Supplementary Figures and Tables from TFE3 Xp11.2 Translocation Renal Cell Carcinoma Mouse Model Reveals Novel Therapeutic Targets and Identifies GPNMB as a Diagnostic Marker for Human Disease

Author

Baba, Masaya, primary, Furuya, Mitsuko, primary, Motoshima, Takanobu, primary, Lang, Martin, primary, Funasaki, Shintaro, primary, Ma, Wenjuan, primary, Sun, Hong-Wei, primary, Hasumi, Hisashi, primary, Huang, Ying, primary, Kato, Ikuma, primary, Kadomatsu, Tsuyoshi, primary, Satou, Yorifumi, primary, Morris, Nicole, primary, Karim, Baktiar O., primary, Ileva, Lilia, primary, Kalen, Joseph D., primary, Wilan Krisna, Luh Ade, primary, Hasumi, Yukiko, primary, Sugiyama, Aiko, primary, Kurahashi, Ryoma, primary, Nishimoto, Koshiro, primary, Oyama, Masafumi, primary, Nagashima, Yoji, primary, Kuroda, Naoto, primary, Araki, Kimi, primary, Eto, Masatoshi, primary, Yao, Masahiro, primary, Kamba, Tomomi, primary, Suda, Toshio, primary, Oike, Yuichi, primary, Schmidt, Laura S., primary, and Linehan, W. Marston, primary

Published
2023
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26. MP41-14 PROGNOSTIC IMPACT AND GENOMIC BACKGROUNDS OF RENAL PARENCHYMAL INFILTRATION OR MICRONODULAR SPREAD IN CLEAR CELL RENAL CELL CARCINOMA

Author

Tanaka, Hajime, primary, Fukawa, Yuki, additional, Yamamoto, Kouhei, additional, Tanimoto, Kousuke, additional, Takemoto, Akira, additional, Hasumi, Hisashi, additional, Hirakawa, Akihiro, additional, Ishikawa, Yudai, additional, Fukuda, Shohei, additional, Waseda, Yuma, additional, Yoshida, Soichiro, additional, Yokoyama, Minato, additional, Campbell, Steven C., additional, and Fujii, Yasuhisa, additional

Published
2023
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28. FDG PET/CT after first molecular targeted therapy predicts survival of patients with renal cell carcinoma

Author

Nakaigawa, Noboru, Kondo, Keiichi, Kaneta, Tomohiro, Tateishi, Ukihide, Minamimoto, Ryogo, Namura, Kazuhiro, Ueno, Daiki, Kobayashi, Kazuki, Kishida, Takeshi, Ikeda, Ichiro, Hasumi, Hisashi, Makiyama, Kazuhide, Hayashi, Narihiko, Osaka, Kimito, Muraoka, Kentaro, Izumi, Koji, Kawahara, Takashi, Teranishi, Jun-ichi, Miyoshi, Yasuhide, Yumura, Yasushi, Uemura, Hiroji, Inoue, Tomio, and Yao, Masahiro

Published
2018
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31. Early assessment with 18F-2-fluoro-2-deoxyglucose positron emission tomography/computed tomography to predict short-term outcome in clear cell renal carcinoma treated with nivolumab

Author

Tabei, Tadashi, Nakaigawa, Noboru, Kaneta, Tomohiro, Ikeda, Ichiro, Kondo, Keiichi, Makiyama, Kazuhide, Hasumi, Hisashi, Hayashi, Narihiko, Kawahara, Takashi, Izumi, Koji, Osaka, Kimito, Muraoka, Kentaro, Teranishi, Jun-ichi, Miyoshi, Yasuhide, Yumura, Yasushi, Uemura, Hiroji, Kobayashi, Kazuki, Inoue, Tomio, and Yao, Masahiro

Published
2019
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32. One-month assessment of renal cell carcinoma treated by everolimus using FDG PET/CT predicts progression-free and overall survival

Author

Ito, Hiroki, Kondo, Keiichi, Kawahara, Takashi, Kaneta, Tomohiro, Tateishi, Ukihide, Ueno, Daiki, Namura, Kazuhiro, Kobayashi, Kazuki, Miyoshi, Yasuhide, Yumura, Yasushi, Makiyama, Kazuhide, Hayashi, Narihiko, Hasumi, Hisashi, Osaka, Kimito, Yokomizo, Yumiko, Teranishi, Jun-ichi, Hattori, Yusuke, Inoue, Tomio, Uemura, Hiroji, Yao, Masahiro, and Nakaigawa, Noboru

Published
2017
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35. Targeting chemoresistance in Xp11.2 translocation renal cell carcinoma using a novel polyamide–chlorambucil conjugate

Author

Funasaki, Shintaro, primary, Mehanna, Sally, additional, Ma, Wenjuan, additional, Nishizawa, Hidekazu, additional, Kamikubo, Yasuhiko, additional, Sugiyama, Hiroshi, additional, Ikeda, Shuji, additional, Motoshima, Takanobu, additional, Hasumi, Hisashi, additional, Linehan, W. Marston, additional, Schmidt, Laura S., additional, Ricketts, Chris, additional, Suda, Toshio, additional, Oike, Yuichi, additional, Kamba, Tomomi, additional, and Baba, Masaya, additional

Published
2022
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37. H255Y and K508R missense mutations in tumour suppressor folliculin (FLCN) promote kidney cell proliferation

Author

Hasumi, Hisashi, Hasumi, Yukiko, Baba, Masaya, Nishi, Hafumi, Furuya, Mitsuko, Vocke, Cathy D., Lang, Martin, Irie, Nobuko, Esumi, Chiharu, Merino, Maria J., Kawahara, Takashi, Isono, Yasuhiro, Makiyama, Kazuhide, Warner, Andrew C., Haines, Diana C., Wei, Ming-Hui, Zbar, Berton, Hagenau, Herbert, Feigenbaum, Lionel, Kondo, Keiichi, Nakaigawa, Noboru, Yao, Masahiro, Metwalli, Adam R., Marston Linehan, W., and Schmidt, Laura S.

Published
2017
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38. The folliculin-FNIP1 pathway deleted in human Birt-Hogg-Dubé syndrome is required for murine B-cell development

Author

Baba, Masaya, Keller, Jonathan R., Sun, Hong-Wei, Resch, Wolfgang, Kuchen, Stefan, Suh, Hyung Chan, Hasumi, Hisashi, Hasumi, Yukiko, Kieffer-Kwon, Kyong-Rim, Gonzalez, Carme Gallego, Hughes, Robert M., Klein, Mara E., Oh, Hyoungbin F., Bible, Paul, Southon, Eileen, Tessarollo, Lino, Schmidt, Laura S., Linehan, W. Marston, and Casellas, Rafael

Published
2012
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39. Single-Cell Transcriptomes of Hereditary Kidney Cancers Underscore Genetically Defined Tumor Characteristics and Microenvironment

Author

Jikuya, Ryosuke, primary, Murakami, Koichi, additional, Nishiyama, Akira, additional, Kato, Ikuma, additional, Furuya, Mitsuko, additional, Nakabayashi, Jun, additional, Ramilowski, Jordan A., additional, Hamanoue, Haruka, additional, Maejima, Kazuhiro, additional, Fujita, Masashi, additional, Mitome, Taku, additional, Ohtake, Shinji, additional, Noguchi, Go, additional, Kawaura, Sachi, additional, Odaka, Hisakazu, additional, Kawahara, Takashi, additional, Komeya, Mitsuru, additional, Shinoki, Risa, additional, Ueno, Daiki, additional, Ito, Hiroki, additional, Ito, Yusuke, additional, Muraoka, Kentaro, additional, Hayashi, Narihiko, additional, Kondo, Keiichi, additional, Nakaigawa, Noboru, additional, Hatano, Koji, additional, Baba, Masaya, additional, Suda, Toshio, additional, Kodama, Tatsuhiko, additional, Fujii, Satoshi, additional, Nakagawa, Hidewaki, additional, Tamura, Tomohiko, additional, Makiyama, Kazuhide, additional, Yao, Masahiro, additional, Shuch, Brian M., additional, Schmidt, Laura S., additional, Linehan, W. Marston, additional, and Hasumi, Hisashi, additional

Published
2022
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41. The perioperative outcomes of robot-assisted radical cystectomy with intracorporeal urinary diversion compared with laparoscopic radical cystectomy with extracorporeal urinary diversion at a single institution.

Author

Suzuki, Atsuto, primary, Muraoka, Kentaro, additional, Tatenuma, Tomoyuki, additional, Osaka, Kimito, additional, Yokomizo, Yumiko, additional, Hayashi, Narihiko, additional, Hasumi, Hisashi, additional, Ito, Yusuke, additional, Kondo, Keichi, additional, Nakaigawa, Noboru, additional, and Makiyama, Kazuhide, additional

Published
2021
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47. Folliculin Regulates Osteoclastogenesis Through Metabolic Regulation

Author

Baba, Masaya, Endoh, Mitsuhiro, Ma, Wenjuan, Toyama, Hirofumi, Hirayama, Akiyoshi, Nishikawa, Keizo, Takubo, Keiyo, Hano, Hiroyuki, Hasumi, Hisashi, Umemoto, Terumasa, Hashimoto, Michihiro, Irie, Nobuko, Esumi, Chiharu, Kataoka, Miho, Nakagata, Naomi, Soga, Tomoyoshi, Yao, Masahiro, Kamba, Tomomi, Minami, Takashi, Ishii, Masaru, and Suda, Toshio

Subjects
OSTEOCLAST, Mice, Knockout, Organelle Biogenesis, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Tumor Suppressor Proteins, Osteoclasts, Original Articles, METABOLISM, OSTEOPOROSIS, Oxidative Phosphorylation, Up-Regulation, TRANSCRIPTION FACTORS, Mice, RAW 264.7 Cells, Bone Marrow, Osteogenesis, Purines, Proto-Oncogene Proteins, FOLLICULIN (FLCN), Animals, Original Article, Signal Transduction
Abstract

Osteoclast differentiation is a dynamic differentiation process, which is accompanied by dramatic changes in metabolic status as well as in gene expression. Recent findings have revealed an essential connection between metabolic reprogramming and dynamic gene expression changes during osteoclast differentiation. However, the upstream regulatory mechanisms that drive these metabolic changes in osteoclastogenesis remain to be elucidated. Here, we demonstrate that induced deletion of a tumor suppressor gene, Folliculin (Flcn), in mouse osteoclast precursors causes severe osteoporosis in 3 weeks through excess osteoclastogenesis. Flcn‐deficient osteoclast precursors reveal cell autonomous accelerated osteoclastogenesis with increased sensitivity to receptor activator of NF‐κB ligand (RANKL). We demonstrate that Flcn regulates oxidative phosphorylation and purine metabolism through suppression of nuclear localization of the transcription factor Tfe3, thereby inhibiting expression of its target gene Pgc1. Metabolome studies revealed that Flcn‐deficient osteoclast precursors exhibit significant augmentation of oxidative phosphorylation and nucleotide production, resulting in an enhanced purinergic signaling loop that is composed of controlled ATP release and autocrine/paracrine purinergic receptor stimulation. Inhibition of this purinergic signaling loop efficiently blocks accelerated osteoclastogenesis in Flcn‐deficient osteoclast precursors. Here, we demonstrate an essential and novel role of the Flcn‐Tfe3‐Pgc1 axis in osteoclastogenesis through the metabolic reprogramming of oxidative phosphorylation and purine metabolism. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR).

Published
2018

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