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発がん研究部

最終更新日 : 2023年8月18日

部の紹介

発がん研究部長　石本崇胤

がんの発生において、遺伝的素因・ウイルス感染・慢性炎症などはリスク因子となることが分かっています。これらの因子はがんの発生起源となる細胞に直接的なダメージを蓄積させるだけでなく、周辺環境をダイナミックに変化させます。これまでの研究から、がん細胞と周囲に存在する免疫細胞や線維芽細胞など腫瘍微小環境との相互作用によって、がん進展および治療抵抗性が引き起こされることが明らかになっています。がんを多様性に富む組織として捉え、複数のターゲットを同時に狙い撃つことで相互作用を遮断し、がんの根治を目指します。

研究内容

  1. 腫瘍線維化メカニズムの解明
  2. 腫瘍間質（ストローマ）を標的としたがん治療戦略・バイオマーカーの確立
  3. がん発生期における組織幹細胞とがん幹細胞に関する研究
  4. 多臓器連関が引き起こすがん進展機序の解明

代表論文

Akiyama T, Yasuda T, Uchihara T, Yasuda-Yoshihara N, Tan BJY, Yonemura A, Semba T, Yamasaki J, Komohara Y, Ohnishi K, Wei F, Fu L, Zhang J, Kitamura F, Yamashita K, Eto K, Iwagami S, Tsukamoto H, Umemoto T, Masuda M, Nagano O, Satou Y, Saya H, Tan P, Baba H, Ishimoto T (*corresponding author).
Stromal reprogramming through dual PDGFRα/β blockade boosts the efficacy of anti-PD-1 immunotherapy in fibrotic tumors.
Cancer Res. 2023 Mar 2;83(5):753-770.
Kumar V, Ramnarayanan K, Sundar R, Padmanbahan N, Srivastava S, Koiwa M, Yasuda T, Koh V, Huang K, Tay S, Ho S, Tan A, Ishimoto T, Kim G, Shabbir A, Chen Q, Biyan Z, Xu S, Lam K, Lum H, Teh M, Yong W, So J and Tan P.
Single-cell atlas of lineage states, tumor microenvironment and subtype-specific expression programs in gastric cancer.
Cancer Discov. 2022 Mar 1;12(3):670-691.
Itoyama R, Yasuda-Yoshihara N, Kitamura F, Yasuda T, Bu L, Yonemura A, Uchihara T, Arima K, Hu X, Jun Z, Okamoto Y, Akiyama T, Yamashita K, Nakao Y, Yusa T, Kitano Y, Higashi T, Miyata T, Imai K, Hayashi H, Yamashita YI, Mikawa T, Kondoh H, Baba H, Ishimoto T (*corresponding author).
Metabolic shift to serine biosynthesis through 3-PG accumulation and PHGDH induction promotes tumor growth in pancreatic cancer.
Cancer Lett. 2021 Dec 28;523:29-42.
Yasuda T, Koiwa M, Yonemura A, Miyake K, Kariya R, Kubota S, Yokomizo-Nakano T, Yasuda-Yoshihara N, Uchihara T, Itoyama R, Bu L, Fu L, Arima K, Izumi D, Iwagami S, Eto K, Iwatsuki M, Baba Y, Yoshida N, Ohguchi H, Okada S, Matsusaki K, Sashida G, Takahashi A, Tan P, Baba H*, Ishimoto T*. (*corresponding author)
Inflammation-driven senescence-associated secretory phenotype in cancer-associated fibroblasts enhances peritoneal dissemination.
Cell Rep. 2021 Feb 23;34(8):108779.
Uchihara T, Miyake K, Yonemura A, Komohara Y, Itoyama R, Koiwa M, Yasuda T, Arima K, Harada K, Eto K, Hayashi H, Iwatsuki M, Iwagami S, Baba Y, Yoshida N, Yashiro M, Masuda M, Ajani JA, Tan P, Baba H*, Ishimoto T*. (*corresponding author)
Extracellular Vesicles from Cancer-Associated Fibroblasts Containing Annexin A6 Induces FAK-YAP Activation by Stabilizing β1 Integrin, Enhancing Drug Resistance.
Cancer Res. 2020 Aug 15;80(16):3222-3235.
Arima K, Ohmuraya M, Miyake K, Koiwa M, Uchihara T, Izumi D, Gao F, Yonemura A, Bu L, Okabe H, Imai K, Baba Y, Chikamoto A, Yamashita YI, Furukawa T, Araki K, Baba H*, Ishimoto T*. (*corresponding author)
Inhibition of 15-PGDH causes Kras-driven tumor expansion through prostaglandin E2-ALDH1 signaling in the pancreas.
Oncogene. 2019 Feb;38(8):1211-1224.
Eto T, Miyake K, Nosho K, Ohmuraya M, Imamura Y, Arima K, Kanno S, Fu L, Kiyozumi Y, Izumi D, Sugihara H, Hiyoshi Y, Miyamoto Y, Sawayama H, Iwatsuki M, Baba Y, Yoshida N, Furukawa T, Araki K, Baba H*, Ishimoto T*. (*corresponding author)
Impact of loss-of-function mutations at the RNF43 locus on colorectal cancer development and progression.
J Pathol. 2018 Aug;245(4):445-455.
Izumi D, Ishimoto T* (*corresponding author), Miyake K, Eto T, Arima K, Kiyozumi Y, Kurashige J, Iwatsuki M, Baba Y, Sakamoto Y, Miyamoto Y, Yoshida N, Watanabe M, Takamori H, Tan P, Baba H.
Colorectal cancer stem cells acquire chemoresistance through the upregulation of FBXW7 and the consequent degradation of c-Myc.
Stem Cells 2017 Sep;35(9):2027-2036.
Ishimoto T, Miyake K, Nandi T, Yashiro M, Onishi N, Huang KK, Lin SJ, Kalpana R, Tay ST, Suzuki Y, Cho BC, Kuroda D, Arima K, Izumi D, Iwatsuki M, Baba Y, Oki E, Watanabe M, Saya H, Hirakawa K, Baba H*, Tan P*.
Activation of Transforming Growth Factor Beta 1 Signaling in Gastric Cancer-associated Fibroblasts Increases Their Motility, via Expression of Rhomboid 5 Homolog 2, and Ability to Induce Invasiveness of Gastric Cancer Cells.
Gastroenterology. 2017 Jul;153(1):191-204.
Sawayama H, Ishimoto T (As co-first author), Watanabe M, Yoshida N, Sugihara H, Kurashige J, Hirashima K, Iwatsuki M, Baba Y, Oki E, Morita M, Shiose Y, Baba H*.
Small molecule agonists of PPAR-γ exert therapeutic effects in esophageal cancer.
Cancer Res. 2014 Jan 15; 74(2):575-85.
Mima K, Okabe H, Ishimoto T, Hayashi H, Nakagawa S, Kuroki H, Watanabe M, Beppu T, Tamada M, Nagano O, Saya H, Baba H*.
CD44s regulates the TGF-β-mediated mesenchymal phenotype and is associated with poor prognosis in patients with hepatocellular carcinoma.
Cancer Res. 2012 Jul 1;72 (13):3414-23.
Yae T, Tsuchihashi K, Ishimoto T, Motohara T, Yoshikawa M, Yoshida GJ, Wada T, Masuko T, Mogushi K, Tanaka H, Osawa T, Kanki Y, Minami T, Aburatani H, Ohmura M, Kubo A, Suematsu M, Takahashi K, Saya H and Nagano O*.
Alternative splicing of CD44 mRNA by ESRP1 enhances lung colonization of metastatic cancer cell.
Nat. Commun. 2012 Jun 6;3:883.
Ishimoto T, Nagano O*, Yae T, Tamada M, Motohara T, Oshima H, Oshima M, Ikeda T, Asaba R, Yagi H, Masuko T, Shimizu T, Ishikawa T, Kai K, Takahashi E, Imamura Y, Baba Y, Ohmura M, Suematsu M, Baba H, Saya H.
CD44 Variant Regulates Redox Status in Cancer Cells by Stabilizing the xCT Subunit of System xc- and Thereby Promotes Tumor Growth.
Cancer Cell 2011 Mar 8;19(3):387-400.
Ishimoto T, Oshima H, Oshima M, Kai K, Torii R, Masuko T, Baba H, Saya H, Nagano O*.
CD44+ slow-cycling tumor cell expansion is triggered by the cooperative actions of Wnt and prostaglandin E2 in gastric tumorigenesis.
Cancer Sci. 2010 March; 101(3): 673-678.

連絡先

〒135-8550　
東京都江東区有明3-8-31
公益財団法人 がん研究会
TEL:　03-3570-0462
E-mail: takatsugu.ishimoto@jfcr.or.jp

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