Functional analysis of SHARPIN and PRMT5 in clear cell sarcoma

• Project/Area Number: 18K16639
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Osaka International Cancer Institute
• Principal Investigator: Tamiya Hironari 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, リハビリテーション科 部長 (70811686)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 悪性骨軟部腫瘍 / フェロトーシス / SHARPIN / 悪性軟部腫瘍 / 淡明細胞肉腫 / PRMT5

Outline of Final Research Achievements

TCGA dataset of soft tissue sarcoma 265 cases showed that high SHARPIN expression is associated with poor prognosis. SHARPIN inhibition enhanced resistance against ferroptosis. Further investigation will be warranted to clarify the sensitivity of ferroptosis on sarcoma entities with high SHARPIN expression which is correlated with poor prognosis.

Academic Significance and Societal Importance of the Research Achievements

悪性骨軟部腫瘍（肉腫）は難治性希少がんであり有効な化学療法が少なく新たな治療薬の開発が強く望まれている。本研究にてSHARPINと予後不良との関連および鉄依存性細胞死フェロトーシスへの関与を解明できた。本研究を礎にして、今後肉腫における新規抗がん剤治療としてフェロトーシスの有効性を明らかにし肉腫患者の予後を改善させるため臨床応用を目指したい。

Research Products

• [Journal Article] Primary breast angiosarcoma with disseminated intravascular coagulation is successfully treated with self?subcutaneous unfractionated heparin calcium injection: A case report (2021)
  • Author(s): Yagi Toshinari、Nakamura Harumi、Wakamatsu Toru、Imura Yoshinori、Tamiya Hironari、Sabe Hideaki、Yamashita Katsunari、Watanabe Makiyo、Takenaka Satoshi
  • Journal Title: Molecular and Clinical Oncology Volume: 14 Issue: 5 Pages: 104-104
  • DOI: 10.3892/mco.2021.2266
  • Peer Reviewed / Open Access
• [Journal Article] Malignant gastrointestinal neuroectodermal tumor with BRAF mutation and a history of malignant melanoma: A case report (2020)
  • Author(s): Yagi Toshinari、Nagata Shigenori、Yamamoto Takashi、Wakamatsu Toru、Imura Yoshinori、Tamiya Hironari、Sabe Hideaki、Yamashita Katsunari、Takenaka Satoshi
  • Journal Title: Molecular and Clinical Oncology Volume: 14 Issue: 2 Pages: 1-7
  • DOI: 10.3892/mco.2020.2185
  • Peer Reviewed / Open Access
• [Journal Article] Eribulin Provides a Remarkable Effect in Trabectedin-Resistant Myxoid Liposarcoma (2020)
  • Author(s): Tamiya Hironari、Sabe Hideaki、Yamashita Katsunari、Imura Yoshinori、Wakamatsu Toru、Takenaka Satoshi
  • Journal Title: Case Reports in Orthopedics Volume: 2020 Pages: 1-7
  • DOI: 10.1155/2020/8873185
  • Peer Reviewed / Open Access
• [Journal Article] A case of Stewart?Treves syndrome occurring in the abdominal wall successfully treated with eribulin: A case report (2020)
  • Author(s): Imura Yoshinori、Nagata Shigenori、Wakamatsu Toru、Tanaka Takaaki、Tamiya Hironari、Naka Norifumi、Takenaka Satoshi
  • Journal Title: Molecular and Clinical Oncology Volume: 13 Issue: 5 Pages: 1-1
  • DOI: 10.3892/mco.2020.2119
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic factors and skeletal?related events in patients with bone metastasis from gastric cancer (2020)
  • Author(s): Imura Yoshinori、Tateiwa Daisuke、Sugimoto Naotoshi、Inoue Akitomo、Wakamatsu Toru、Outani Hidetatsu、Tanaka Takaaki、Tamiya Hironari、Yagi Toshinari、Naka Norifumi、Okawa Sumiyo、Tabuchi Takahiro、Takenaka Satoshi
  • Journal Title: Molecular and Clinical Oncology Volume: 13 Pages: 1-8
  • DOI: 10.3892/mco.2020.2101
  • Peer Reviewed / Open Access
• [Journal Article] PRMT5 control of cGAS/STING and NLRC5 pathways defines melanoma response to antitumor immunity (2020)
  • Author(s): Kim Hyungsoo、Kim Heejung、Feng Yongmei、Li Yan、Tamiya Hironari、Tocci Stefania、Ronai Ze’ev A.
  • Journal Title: Science Translational Medicine Volume: 12 Issue: 551
  • DOI: 10.1126/scitranslmed.aaz5683
  • Peer Reviewed
• [Journal Article] A long‐term follow‐up study of extracorporeal irradiated autografts in limb salvage surgery for malignant bone and soft tissue tumors: A minimum follow‐up of 10 years after surgery (2020)
  • Author(s): Outani Hidetatsu、Takenaka Satoshi、Hamada Kenichiro、Imura Yoshinori、Kakunaga Shigeki、Tamiya Hironari、Wakamatsu Toru、Naka Norifumi、Ueda Takafumi、Araki Nobuhito
  • Journal Title: Journal of Surgical Oncology Volume: 121 Issue: 8 Pages: 1276-1282
  • DOI: 10.1002/jso.25918
  • Peer Reviewed
• [Journal Article] Clinical outcomes and significant factors in the survival rate after decompression surgery for patients who were non-ambulatory due to spinal metastases (2019)
  • Author(s): Tateiwa Daisuke、Oshima Kazuya、Nakai Takaaki、Imura Yoshinori、Tanaka Takaaki、Outani Hidetatsu、Tamiya Hironari、Araki Nobuhito、Naka Norifumi
  • Journal Title: Journal of Orthopaedic Science Volume: 24 Issue: 2 Pages: 347-352
  • DOI: 10.1016/j.jos.2018.10.003
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Survival analysis of elderly patients with osteosarcoma (2019)
  • Author(s): Imura Yoshinori、Takenaka Satoshi、Kakunaga Shigeki、Nakai Takaaki、Wakamatsu Toru、Outani Hidetatsu、Tanaka Takaaki、Tamiya Hironari、Oshima Kazuya、Hamada Kenichiro、Naka Norifumi、Araki Nobuhito、Kudawara Ikuo、Ueda Takafumi、Yoshikawa Hideki
  • Journal Title: International Orthopaedics Volume: 43 Issue: 7 Pages: 1741-1747
  • DOI: 10.1007/s00264-019-04332-y
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Favorable outcomes of localized synovial sarcoma patients with a high utilization rate of neoadjuvant and/or adjuvant chemotherapy (2019)
  • Author(s): Outani Hidetatsu、Kakunaga Shigeki、Hamada Kenichiro、Takenaka Satoshi、Imura Yoshinori、Nagata Shigenori、Tanaka Takaaki、Tamiya Hironari、Oshima Kazuya、Naka Norifumi、Kudawara Ikuo、Araki Nobuhito、Ueda Takafumi、Yoshikawa Hideki
  • Journal Title: Molecular and Clinical Oncology Volume: 11 Pages: 151-156
  • DOI: 10.3892/mco.2019.1863
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Establishment of a novel human CIC-DUX4 sarcoma cell line, Kitra-SRS, with autocrine IGF-1R activation and metastatic potential to the lungs (2019)
  • Author(s): Nakai Sho、Yamada Shutaro、Outani Hidetatsu、Nakai Takaaki、Yasuda Naohiro、Mae Hirokazu、Imura Yoshinori、Wakamatsu Toru、Tamiya Hironari、Tanaka Takaaki、Hamada Kenichiro、Tani Akiyoshi、Myoui Akira、Araki Nobuhito、Ueda Takafumi、Yoshikawa Hideki、Takenaka Satoshi、Naka Norifumi
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 15812-15812
  • DOI: 10.1038/s41598-019-52143-3
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Eribulin Suppresses Clear Cell Sarcoma Growth by Inhibiting Cell Proliferation and Inducing Melanocytic Differentiation Both Directly and Via Vascular Remodeling (2019)
  • Author(s): Nakai Sho、Tamiya Hironari、Imura Yoshinori、Nakai Takaaki、Yasuda Naohiro、Wakamatsu Toru、Tanaka Takaaki、Outani Hidetatsu、Takenaka Satoshi、Hamada Kenichiro、Myoui Akira、Araki Nobuhito、Ueda Takafumi、Yoshikawa Hideki、Naka Norifumi
  • Journal Title: Molecular Cancer Therapeutics Volume: 19 Issue: 3 Pages: 742-754
  • DOI: 10.1158/1535-7163.mct-19-0358
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clinical features and prognostic factors in patients with esophageal cancer with bone metastasis (2019)
  • Author(s): Imura Yoshinori、Yamamoto Sachiko、Wakamatsu Toru、Tanaka Takaaki、Tamiya Hironari、Sugimura Keijiro、Miyata Hiroshi、Ishihara Ryu、Yano Masahiko、Naka Norifumi
  • Journal Title: Oncology Letters Volume: 19 Pages: 717-724
  • DOI: 10.3892/ol.2019.11142
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Malignant peripheral nerve?sheath tumors in an adolescent patient with mosaic localized NF1: A case report (2019)
  • Author(s): Hagizawa Hiroki、Nagata Shigenori、Wakamatsu Toru、Imura Yoshinori、Tanaka Takaaki、Outani Hidetatsu、Konishi Eiichi、Naka Norifumi、Tamiya Hironari
  • Journal Title: Molecular and Clinical Oncology Volume: 12 Pages: 155-159
  • DOI: 10.3892/mco.2019.1969
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Posterior Positioning of a Clavicle Hook Plate Is a Risk Factor for Acromial Fractures after Acromioclavicular Joint Dislocation (2019)
  • Author(s): Tamiya Hironari、Umemoto Shusaku、Akimoto Yasuyoshi、Kyo Takayuki、Gamo Kazushige、Kuratsu Shigeyuki
  • Journal Title: Open Journal of Orthopedics Volume: 09 Issue: 04 Pages: 101-111
  • DOI: 10.4236/ojo.2019.94010
  • Peer Reviewed / Open Access
• [Journal Article] Endoprosthetic Reconstruction for a Displaced Atypical Femoral Fracture in a Cancer Patient with Poor Prognosis (2018)
  • Author(s): Tamiya Hironari、Hagizawa Hiroki、Nakai Takaaki、Imura Yoshinori、Tanaka Takaaki、Oshima Kazuya、Ito Toshikazu、Naka Norifumi、Kuratsu Shigeyuki
  • Journal Title: Case Reports in Orthopedics Volume: 2018 Pages: 1-5
  • DOI: 10.1155/2018/7862516
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Features and Prognosis of Patients With the Bone Metastasis of Pancreatic Cancer (2018)
  • Author(s): Outani Hidetatsu、Akita Hirofumi、Nakai Takaaki、Takada Ryoji、Imura Yoshinori、Tanaka Takaaki、Tamiya Hironari、Oshima Kazuya、Takahashi Hidenori、Ohkawa Kazuyoshi、Katayama Kazuhiro、Araki Nobuhito、Naka Norifumi
  • Journal Title: Pancreas Volume: 47 Issue: 7 Pages: e43-e46
  • DOI: 10.1097/mpa.0000000000001098
  • Peer Reviewed
• [Journal Article] Calcific myonecrosis mimicking soft tissue sarcoma: A case report (2018)
  • Author(s): Ukon Yuichiro、Tanaka Takaaki、Nagata Shigenori、Hagizawa Hiroki、Imura Yoshinori、Tamiya Hironari、Oshima Kazuya、Naka Norifumi、Aoki Yasuaki、Kuratsu Shigeyuki
  • Journal Title: Oncology Letters Volume: 15 Pages: 7909-7913
  • DOI: 10.3892/ol.2018.8320
  • Peer Reviewed / Open Access
• [Presentation] 80歳以上の超高齢者と 60-79 歳の高齢者における悪性軟部腫瘍の背景因子，治療因子，予後の違いについての検討 (2020)
  • Author(s): 田宮大也 角永茂樹 濱田健一郎 王谷英達 伊村慶紀 若松透 竹中聡
  • Organizer: 第53回日本整形外科学会骨・軟部腫瘍学術集会
• [Presentation] Investigation of ferroptosis as a therapeutic target and the role of SHARPIN in sarcoma (2020)
  • Author(s): 田宮大也 若松透 竹中聡
  • Organizer: 第79回日本癌学会学術総会
• [Presentation] 術後10年以上経過して隣接骨に再発した軟骨肉腫の1例 (2020)
  • Author(s): 田宮大也、伊村慶紀，若松透，田中太晶，中 紀文
  • Organizer: 第3回日本サルコーマ治療研究学会学術集会
• [Presentation] Investigation of ferroptosis as a therapeutic target and the role of SHARPIN-PRMT5 axis in sarcoma (2020)
  • Author(s): Hironari Tamiya, Akitomo Inoue, Yoshinori Imura, Toru Wakamatsu, Takaaki Tanaka, Norifumi Naka
  • Organizer: Orthopaedic Research Society 2020 Annual Meeting
  • Int'l Joint Research
• [Presentation] 骨軟部腫瘍に対する遺伝子診断の当院での取り組み (2020)
  • Author(s): 田宮大也、伊村慶紀，若松透，田中太晶，中 紀文
  • Organizer: 第134回中部日本整形外科災害外科学会・学術集会
  • Invited
• [Presentation] 悪性骨軟部腫瘍治療におけるferroptosis有用性の検討 (2019)
  • Author(s): 田宮大也、田中太晶，若松透、伊村慶紀，中 紀文
  • Organizer: 第34回日本整形外科学会基礎学術集会
• [Presentation] トラベクテジン抵抗性粘液型脂肪肉腫に対しエリブリンが著効した1例 (2019)
  • Author(s): 田宮大也、喜多洸介，伊村慶紀，若松透，田中太晶，中 紀文
  • Organizer: 第2回日本日本サルコーマ治療研究学会学術集会
• [Presentation] 当科で治療した淡明細胞肉腫の治療成績 (2018)
  • Author(s): 田宮大也、萩澤宏樹，中井隆彰，田中太晶，伊村慶紀，大島和也．中 紀文
  • Organizer: 第51回日本整形外科学会骨・軟部腫瘍学術集会