Degree 【 display / non-display 】

Degree 【 display / non-display 】

• M.D., Ph.D.

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2012.08

  -

  Now

  Sapporo Medical University   School of Medicine, Department of Molecular Biorogy   教授

  教授

• 2011.07

  -

  2012.07

  Sapporo Medical University   School of Medicine, Department of Molecular Biorogy   助教

  助教

• 2007.04

  -

  2011.06

  Sapporo Medical University   医学部内科学第一講座   助教

  助教

• 2004.04

  -

  2007.03

  Sapporo Medical University   School of Medicine, Dept.of Public Health   助手

  助手

• 2000.05

  -

  2003.11

  Johns Hopkins University   Oncology Center   Postdoctoral fellow

  Postdoctoral fellow

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 　

  　

  　

  日本癌学会

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  Japan Society for Molecular Tumor Marker Research

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  日本分子生物学会

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  日本分子腫瘍マーカー研究会

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  American Association for Cancer Reserach

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Tumor biology  

• Life sciences   Tumor diagnostics and therapeutics  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   School of Medicine, Dept. of Molecular Biology   Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 内科

• 癌

• エピジェネティクス

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• LINC02154 promotes cell cycle and mitochondrial function in oral squamous cell carcinoma.

  Takeshi Niinuma, Hiroshi Kitajima, Tatsuya Sato, Toshifumi Ogawa, Kazuya Ishiguro, Masahiro Kai, Eiichiro Yamamoto, Yui Hatanaka, Iyori Nojima, Mutsumi Toyota, Akira Yorozu, Shohei Sekiguchi, Noritsugu Tohse, Masato Furuhashi, Hiroshi Ohguro, Akihiro Miyazaki, Hiromu Suzuki

  Cancer science    2024.11  [International journal]

  　View Summary

  Long noncoding RNAs (lncRNAs) play pivotal roles in the development of human malignancies, though their involvement in oral squamous cell carcinoma (OSCC) remains incompletely understood. Using The Cancer Genome Atlas (TCGA) dataset, we analyzed expression of 7840 lncRNAs in primary head and neck squamous cell carcinoma (HNSCC) and found that upregulation of LINC02154 is associated with a poorer prognosis. LINC02154 knockdown in OSCC cell lines induced cell cycle arrest and apoptosis, and significantly attenuated tumor growth in vitro and in vivo. Notably, depletion of LINC02154 downregulated FOXM1, a master regulator of cell cycle-related genes. RNA pulldown and mass spectrometry analyses identified a series of proteins that could potentially interact with LINC02154, including HNRNPK and LRPPRC. HNRNPK stabilizes FOXM1 expression by interacting with the 3'-UTR of FOXM1 mRNA, which suggests LINC02154 and HNRNPK promote cell cycling by regulating FOXM1 expression. Additionally, LINC02154 positively regulates HNRNPK expression by inhibiting microRNAs targeting HNRPNK. Moreover, LINC02154 affects mitochondrial function by interacting with LRPPRC. Depletion of LINC02154 suppressed expression of mitochondrial genes, including MTCO1 and MTCO2, and inhibited mitochondrial respiratory function in OSCC cells. These results suggest that LINC02154 exerts its oncogenic effects by modulating the cell cycle and oxidative phosphorylation in OSCC, highlighting LINC02154 as a potential therapeutic target.

  DOI PubMed

• AEBP1 is a negative regulator of skeletal muscle cell differentiation in oral squamous cell carcinoma.

  Fumika Okazaki, Akira Yorozu, Shohei Sekiguchi, Takeshi Niinuma, Reo Maruyama, Hiroshi Kitajima, Eiichiro Yamamoto, Kazuya Ishiguro, Mutsumi Toyota, Yui Hatanaka, Koyo Nishiyama, Kazuhiro Ogi, Masahiro Kai, Kenichi Takano, Shingo Ichimiya, Akihiro Miyazaki, Hiromu Suzuki

  Scientific reports   14 ( 1 ) 27425 - 27425  2024.11  [International journal]

  　View Summary

  The tumor microenvironment plays a pivotal role in cancer development. We recently reported that in oral squamous cell carcinoma (OSCC), adipocyte enhancer-binding protein 1 (AEBP1) is abundantly expressed in cancer-associated fibroblasts (CAFs), leading to CAF activation and inhibition of CD8 + T cell infiltration. In the present study, we investigated whether AEBP1 contributes to the destruction and atrophy of muscle tissues in OSCC. By analyzing human skeletal muscle myoblasts (HSMMs), we found that AEBP1 is downregulated during muscle cell differentiation. Transcriptome analysis revealed that AEBP1 knockdown significantly upregulates myogenesis-related genes in HSMMs, and qRT-PCR and western blot analyses confirmed the induction of muscle-related genes, including MYOG, in HSMMs after AEBP1 knockdown. Conversely, ectopic expression of AEBP1 strongly suppressed myogenesis-related genes in HSMMs. Notably, indirect co-culture of HSMMs with OSCC cells led to AEBP1 upregulation and robust suppression of muscle-related genes in HSMMs. Treatment with TGF-β1 also upregulated AEBP1 and suppressed expression of muscle-related genes in HSMMs. Our findings suggest that AEBP1 is a negative regulator of skeletal muscle cell differentiation and that OSCC cells inhibit muscle cell differentiation, at least in part, by inducing AEBP1.

  DOI PubMed

• Serial single-cell RNA sequencing unveils drug resistance and metastatic traits in stage IV breast cancer.

  Kazutaka Otsuji, Yoko Takahashi, Tomo Osako, Takayuki Kobayashi, Toshimi Takano, Sumito Saeki, Liying Yang, Satoko Baba, Kohei Kumegawa, Hiromu Suzuki, Tetsuo Noda, Kengo Takeuchi, Shinji Ohno, Takayuki Ueno, Reo Maruyama

  NPJ precision oncology   8 ( 1 ) 222 - 222  2024.10  [International journal]

  　View Summary

  Metastasis is a complex process that remains poorly understood at the molecular levels. We profiled single-cell transcriptomic, genomic, and epigenomic changes associated with cancer cell progression, chemotherapy resistance, and metastasis from a Stage IV breast cancer patient. Pretreatment- and posttreatment-specimens from the primary tumor and distant metastases were collected for single-cell RNA sequencing and subsequent cell clustering, copy number variation (CNV) estimation, transcriptomic factor estimation, and pseudotime analyses. CNV analysis revealed that a small population of pretreatment cancer cells resisted chemotherapy and expanded. New clones including Metastatic Precursor Cells (MPCs), emerged in the posttreatment primary tumors in CNV similar to metastatic cells. MPCs exhibited expression profiles indicative of epithelial-mesenchymal transition. Comparison of MPCs with metastatic cancer cells also revealed dynamic changes in transcription factors and calcitonin pathway gene expression. These findings demonstrate the utility of single-patient clinical sample analysis for understanding tumor drug resistance, regrowth, and metastasis.

  DOI PubMed

• Application of Single Cell Type-Derived Spheroids Generated by Using a Hanging Drop Culture Technique in Various In Vitro Disease Models: A Narrow Review.

  Hiroshi Ohguro, Megumi Watanabe, Tatsuya Sato, Nami Nishikiori, Araya Umetsu, Megumi Higashide, Toshiyuki Yano, Hiromu Suzuki, Akihiro Miyazaki, Kohichi Takada, Hisashi Uhara, Masato Furuhashi, Fumihito Hikage

  Cells   13 ( 18 )  2024.09  [International journal]

  　View Summary

  Cell culture methods are indispensable strategies for studies in biological sciences and for drug discovery and testing. Most cell cultures have been developed using two-dimensional (2D) culture methods, but three-dimensional (3D) culture techniques enable the establishment of in vitro models that replicate various pathogenic conditions and they provide valuable insights into the pathophysiology of various diseases as well as more precise results in tests for drug efficacy. However, one difficulty in the use of 3D cultures is selection of the appropriate 3D cell culture technique for the study purpose among the various techniques ranging from the simplest single cell type-derived spheroid culture to the more sophisticated organoid cultures. In the simplest single cell type-derived spheroid cultures, there are also various scaffold-assisted methods such as hydrogel-assisted cultures, biofilm-assisted cultures, particle-assisted cultures, and magnet particle-assisted cultures, as well as non-assisted methods, such as static suspension cultures, floating cultures, and hanging drop cultures. Since each method can be differently influenced by various factors such as gravity force, buoyant force, centrifugal force, and magnetic force, in addition to non-physiological scaffolds, each method has its own advantages and disadvantages, and the methods have different suitable applications. We have been focusing on the use of a hanging drop culture method for modeling various non-cancerous and cancerous diseases because this technique is affected only by gravity force and buoyant force and is thus the simplest method among the various single cell type-derived spheroid culture methods. We have found that the biological natures of spheroids generated even by the simplest method of hanging drop cultures are completely different from those of 2D cultured cells. In this review, we focus on the biological aspects of single cell type-derived spheroid culture and its applications in in vitro models for various diseases.

  DOI PubMed

• Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas.

  Hironori Aoki, Akira Takasawa, Eiichiro Yamamoto, Takeshi Niinuma, Hiro-O Yamano, Taku Harada, Toshiyuki Kubo, Akira Yorozu, Hiroshi Kitajima, Kazuya Ishiguro, Masahiro Kai, Akio Katanuma, Toshiya Shinohara, Hiroshi Nakase, Tamotsu Sugai, Makoto Osanai, Hiromu Suzuki

  BMC gastroenterology   24 ( 1 ) 91 - 91  2024.03  [International journal]

  　View Summary

  BACKGROUND: Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions. METHODS: SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112). RESULTS: SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components. CONCLUSION: Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• Epigenetic alteration of SALL3 contributes to chemoresistance in triple-negative breast cancer

  Yosuke Matsushita, Masato Komatsu, Kazuma Kiyotani, Takeshi Niinuma, Hiromu Suzuki, Tetsuro Yoshimaru, Atsushi Tajima, Issei Imoto, Junko Honda, Yoichi Furukawa, Yusuke Nakamura, Yasuo Miyoshi, Mitsunori Sasa, Toyomasa Katagiri

  CANCER SCIENCE ( WILEY )  113   752 - 752  2022.02

  Research paper, summary (international conference)  

• Analysis of AEBP1 in the microenvironment of head and neck squamous cell carcinoma

  Shohei Sekiguchi, Akira Yorozu, Eiichiro Yamamoto, Takeshi Niinuma, Akira Takasawa, Gota Sudo, Kazushige Koike, Yui Hatanaka, Ayano Yoshido, Hiroshi Kitajima, Masahiro Kai, Makoto Osanai, Kenichi Takano, Akihiro Miyazaki, Hiromu Suzuki

  CANCER SCIENCE ( WILEY )  113   1506 - 1506  2022.02

  Research paper, summary (international conference)  

• LOW EXPRESSION OF miRNA-199-5p AND miRNA-374 CAN PREDICT THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH CHRONIC HEPATITIS B AFTER ADMINISTRATION OF NUCLEOSIDE ANALOG.

  Hideaki Takahashi, Chiaki Okuse, Norie Yamada, Takeshi Niinuma, Masahiro Kai, Hideki Wakasugi, Noriyuki Akutsu, Hiroshi Yotsuyanagi, Michihiro Suzuki, Hiromu Suzuki, Fumio Itoh

  HEPATOLOGY ( WILEY )  74   656A - 657A  2021.10

  Research paper, summary (international conference)  

• SMOC1の大腸腫瘍診断マーカーとしての臨床的有用性の検討

  青木 敬則, 山本 英一郎, 高澤 啓, 新沼 猛, 山野 泰穂, 萬 顕, 北嶋 洋志, 甲斐 正広, 小山内 誠, 仲瀬 裕志, 菅井 有, 鈴木 拓

  日本癌学会総会記事 ( (一社)日本癌学会 )  80回   [P14 - 4]  2021.09

• 頭頸部扁平上皮癌の癌微小環境におけるAEBP1の解析

  萬 顕, 山本 圭佑, 小幡 和史, 大國 毅, 黒瀬 誠, 近藤 敦, 高澤 啓, 小島 隆, 鈴木 拓, 高野 賢一

  日本耳鼻咽喉科学会会報 ( (一社)日本耳鼻咽喉科頭頸部外科学会 )  124 ( 4 ) 690 - 690  2021.04

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 田原榮一賞

  2017   日本消化器癌発生学会  

  Winner： 鈴木 拓

• 北海道医師会賞・北海道知事賞

  2016  

  Winner： 鈴木 拓

• 北海道科学技術奨励賞

  2014  

  Winner： 鈴木 拓

• 第19回日本消化器癌発生学会総会最優秀賞

  2008  

  Winner： 鈴木 拓

• 日本臨床分子医学会学術奨励賞

  2005  

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• DOT1L阻害によるインターフェロン応答の機序解明とがん免疫療法への応用

  基盤研究(B)

  Project Year :

  2022.04

  -

  2025.03

   

  鈴木 拓, 仲瀬 裕志, 新沼 猛, 北嶋 洋志

• ジアシルグリセロールキナーゼが関与するがん進行機構の探索

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  甲斐 正広, 鈴木 拓

• 肝芽腫発生モデルを利用したエピゲノム異常がもたらす抗がん剤耐性機序の解明

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  本多 昌平, 北河 徳彦, 鈴木 拓, 田中 祐吉

• 胃がん関連長鎖non-coding RNAによるストレス顆粒と発がん機構の解析

  基盤研究(C)

  Project Year :

  2021.04

  -

  2024.03

   

  北嶋 洋志, 鈴木 拓

  　View Summary

  申請者らは先行実験により慢性胃炎および胃がんで発現が亢進する長鎖non-coding RNA (lncRNA) TM4SF1AS1がストレス顆粒の形成促進とアポトーシスの抑制に関与することを明らかにしたが、その詳細なメカニズムは不明である。本研究はその分子機構を明らかにすることを目的としている。 TM4SF1AS1の詳細な細胞内の局在情報を得るために、MS2タグを付加したTM4SF1AS1のTet-on遺伝子発現誘導系胃がん細胞株を樹立し、免疫蛍光染色を行った。ストレス顆粒マーカーであるTIA-1、G3BP1やG3BP2と共にTM4SF1AS1がその過剰発現によって形成された顆粒様構造に局在することが示された。 また、TM4SF1AS1との相互作用が見られたRACK1は、MTK1の活性化からp38/JNKを介したアポトーシスを引き起こすが、ストレス顆粒はRACK1を顆粒内に隔離しアポトーシスを抑制することが知られる。TM4SF1AS1の過剰発現により形成されたストレス顆粒にRACK1が局在したことから、がん細胞におけるTM4SF1AS1によるストレス顆粒の機能として、生存に不利に働くタンパク質や転写産物を隔離しその機能の阻害や翻訳を抑制することが考えられた。 そこでTM4SF1AS1と相互作用し翻訳抑制を受ける可能性のあるRNA分子の探索を、ChIRP RNA-seqにより試みた。結果585個の候補が得られ、その三分の一がmRNAに該当した。Gene Ontology解析を行った結果、アポトーシスに関連するmRNAがエンリッチしていた。一部のアポトーシス関連mRNAがTM4SF1AS1の標的となり翻訳抑制を受ける可能性があると考えられることから、さらなる解析を進める。

• がん細胞のインターフェロンシグナルを制御する長鎖noncoding RNAの解析

  基盤研究(C)

  Project Year :

  2021.04

  -

  2024.03

   

  新沼 猛, 鈴木 拓

  　View Summary

  消化器癌におけるDLEU1の機能解析を行うために大腸癌細胞株RKO、HCT116、DLD1、SW480を用いてDLEU1をノックダウンし細胞増殖に与える影響についてCCK-8を用いたcell viability assayを行った。大腸癌についてはいずれの細胞株においてもDLEU1のノックダウンは細胞増殖を抑制した。DLEU1のノックダウンがIFNシグナルに与える影響を調べるためにDLD1、SW480においてIFITM1、IFITM3の発現をRT-qPCRにて解析したところ、口腔扁平上皮癌と異なり、これらのISGｓは発現が不変～上昇傾向であった。HCT116においてはDLEU1のノックダウンによりIFITM1は発現低下、IFITM3は発現上昇、RKOにおいてはIFITM1は発現低下が認められた。DLD1、SW480ではIFITM1、IFITM3ともDLEU1のノックダウンにより発現が上昇傾向であった。さらに他の消化器癌においてDLEU1の機能を解析するために食道癌細胞株であるTE5、TE9、TE15を用いてDLEU1をノックダウンし、細胞増殖に与える影響についてcell viability assayを行った。異なるsiRNAを用いて解析したが、食道癌においてはDLEU1のノックダウンにより増殖の亢進、抑制いずれも起こり一定の傾向が認められなかった。ISGｓに与える影響についてもRT-qPCRによりIFITM3、IFITM1の発現も解析したが、発現の上昇・低下いずれも認められ一定の傾向を示さなかった。TE-5においてはIFITM1、IFITM3は発現が低下傾向であったが、TE-9においてはIFITM3は発現が上昇、TE-15はIFITM1の発現が低下傾向であった。

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