Education 【 display / non-display 】

Education 【 display / non-display 】

• 　

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  2003

  Hokkaido University  

Degree 【 display / non-display 】

Degree 【 display / non-display 】

• 博士（薬学）

Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

• 2024.01

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  Now

  Sapporo Medical University   Department of Cell Science, Institute of Cancer Research   Associate Professor

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 2013

  -

  Now

  JAPAN SOCIETY FOR CELL BIOLOGY

• 2013

  -

  Now

  北海道癌談話会

• 2013

  -

  2017

  The Japanese Society of Pathology

• 2007

  -

  Now

  THE JAPANESE CANCER ASSOCIATION

• 2004

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  2013

  The Japanese Biochemical Society

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Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Morphology, anatomy  

• Life sciences   Cell biology  

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   Department of Cell Science, Institute of Cancer Research   Associate Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 上皮細胞

• 細胞極性

• 細胞運動

• トランスレーショナルリサーチ

• ケミカルバイオロジー

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Papers 【 display / non-display 】

Papers 【 display / non-display 】

• Atypical Macropinocytosis Contributes to Malignant Progression: A Review of Recent Evidence in Endometrioid Endometrial Cancer Cells

  Takayuki Kohno, Takashi Kojima

  Cancers    2022.10  [Refereed]

  Authorship：   Lead author  , Corresponding author

  DOI

• Translocation of LSR from tricellular corners causes macropinocytosis at cell–cell interface as a trigger for breaking out of contact inhibition

  Takayuki Kohno, Takumi Konno, Shin Kikuchi, Masuo Kondoh, Takashi Kojima

  The FASEB Journal ( Wiley )  35 ( 9 ) e21742  2021.09  [Refereed]  [International journal]

  Authorship：   Lead author  , Corresponding author

  　View Summary

  Withdrawal from contact inhibition is necessary for epithelial cancer precursor cells to initiate cell growth and motility. Nevertheless, little is understood about the mechanism for the sudden initiation of cell growth under static conditions. We focused on cellular junctions as one region where breaking out of contact inhibition occurs. In well-differentiated endometrial cancer cells, Sawano, the ligand administration for tricellular tight junction protein LSR, which transiently decreased the robust junction property, caused an abrupt increase in cell motility and consequent excessive multilayered cell growth despite being under contact inhibition conditions. We observed that macropinocytosis essentially and temporarily occurred as an antecedent event for the above process at intercellular junctions without disruption of the junction apparatus but not at the apical plasma membrane. Collectively, we concluded that the formation of macropinocytosis, which is derived from tight junction-mediated signaling, was triggered for the initiation of cell growth in static precancerous epithelium.

  DOI PubMed

• A resourceful alteration of tricellular tight junction proteins: roles in endometrial cancer progression.

  Takayuki Kohno

  Tight Junctions: Classification, Structure and Functions.   ISBN: 978-1-53617-327-7  2020.02  [Refereed]

  Authorship：   Lead author  , Corresponding author

• Role of Tricellular Tight Junction Protein Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Cancer Cells.

  Takayuki Kohno, Takumi Konno, Takashi Kojima

  International journal of molecular sciences   20 ( 14 )  2019.07  [Refereed]  [International journal]

  Authorship：   Lead author  , Corresponding author

  　View Summary

  Maintaining a robust epithelial barrier requires the accumulation of tight junction proteins, LSR/angulin-1 and tricellulin, at the tricellular contacts. Alterations in the localization of these proteins temporarily cause epithelial barrier dysfunction, which is closely associated with not only physiological differentiation but also cancer progression and metastasis. In normal human endometrial tissues, the endometrial cells undergo repeated proliferation and differentiation under physiological conditions. Recent observations have revealed that the localization and expression of LSR/angulin-1 and tricellulin are altered in a menstrual cycle-dependent manner. Moreover, it has been shown that endometrial cancer progression affects these alterations. This review highlights the differences in the localization and expression of tight junction proteins in normal endometrial cells and endometrial cancers and how they cause functional changes in cells.

  DOI PubMed

• The bicellular tensile force sorts the localization of LSRs in bicellular and tricellular junctions.

  Takayuki Kohno, Shin Kikuchi, Takafumi Ninomiya, Takashi Kojima

  Annals of the New York Academy of Sciences ( WILEY )  1397 ( 1 ) 185 - 194  2017.06  [Refereed]  [International journal]

  Authorship：   Lead author  , Corresponding author

  　View Summary

  Lipolysis-stimulated lipoprotein receptors (LSRs) localize to tricellular tight junctions. Recent studies have shown that changes in the localization and expression profiles of LSRs are associated with malignancy of endometrial carcinomas, although the precise mechanisms by which malignant progression induces changes in the localization of LSRs are still unknown. In this study, we found that changes in cell tension correlated with alterations in the junctional localization of LSRs in endometrial cancer Sawano cells. At high cell densities, myosin phosphatase target subunit 1 (MYPT1) localized to bicellular junctions, whereas activated myosin regulatory light chain 2 (MRLC2) was dislocated from these regions, suggesting that circumferential tensile forces decreased at high cell densities. Under these conditions, LSRs localized to tricellular junctions. In contrast, a phosphorylated form of MRLC2 localized to bicellular regions, while MYPT1 was excluded from these regions, suggesting that tensile forces formed along the circumferential edge at low cell densities. It is noteworthy that, when cells were cultured under these conditions, LSRs localized to bicellular regions. Upon treatment with a myosin inhibitor, LSR localization in bicellular junctions decreased at low cell densities. Overall, our results indicate that the modulation of cellular tension was involved in the translocation of LSRs from bicellular to tricellular tight junctions.

  DOI PubMed

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• ヒト子宮内膜症のin vitroモデルを用いた新規病態メカニズムの解明

  長尾来夢, 長尾来夢, 幸野貴之, 金野匠, 倉ありさ, 倉ありさ, 斉藤公仁, 嶋田浩志, 齋藤豪, 小島隆

  日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   55th  2023

  J-GLOBAL

• 子宮内膜癌におけるタイト結合分子cingulin(CGN)の役割

  倉ありさ, 倉ありさ, 斉藤公仁, 斉藤公仁, 岡田匡氷, 嶋田浩志, 金野匠, 幸野貴之, 松浦基樹, 齋藤豪, 小島隆

  日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   54th  2022

  J-GLOBAL

• 子宮内膜症,子宮内膜癌細胞におけるAngulin-1/Lipolysis Stimulated Lipoprotein Receptor(LSR)の役割

  斉藤公仁, 斉藤公仁, 嶋田浩志, 金野匠, 倉ありさ, 倉ありさ, 岡田匡氷, 郷久晴朗, 幸野貴之, 松浦基樹, 齋藤豪, 小島隆

  日本臨床分子形態学会総会・学術集会講演プログラム・要旨集   54th  2022

  J-GLOBAL

• タイト結合分子Cluadin-2をターゲットにした子宮内膜癌治療のin vitroにおける検討

  嶋田浩志, 嶋田浩志, 嶋田浩志, 岡田匡氷, 岡田匡氷, 金野匠, 幸野貴之, 松浦基樹, 郷久晴朗, 岩崎雅宏, 小島隆, 齋藤豪

  日本婦人科腫瘍学会雑誌   39 ( 1 )  2021

  J-GLOBAL

• Possibility of tricelluler tight junction LSR/Angulin-1 antibody in therapy for human endometrioid endometrial carcinoma

  斉藤公仁, 幸野貴之, 金野匠, 岡田匡氷, 嶋田浩志, 郷久晴朗, 近藤昌夫, 齋藤豪, 小島隆

  日本分子生物学会年会プログラム・要旨集(Web)   44th  2021

  J-GLOBAL

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Other 【 display / non-display 】

Other 【 display / non-display 】

• 子宮内膜症，子宮内膜癌細胞におけるAngulin-1/Lipolysis Stimulated Lipoprotein Receptor (LSR)の役割

  2022.11

  　

  　

  　View Summary

  斉藤公仁，嶋田浩志，金野匠，倉ありさ，岡田匡氷，郷久晴朗，幸野貴之，松浦基樹，齋藤豪，小島隆，第54回 日本臨床分子形態学会総会・学術集会：シンポジウム講演

• 子宮内膜癌細胞SawanoにおけるLSR-KO細胞の解析に基づく細胞分裂亢進の制御機序

  2022.11

  　

  　

  　View Summary

  幸野貴之，菊池真，倉ありさ，斉藤公仁，齋藤豪，小島隆，第54回 日本臨床分子形態学会総会・学術集会：ワークショップ講演

• 女性ホルモンは3細胞間タイト結合タンパク質の局在変化を伴って細胞の厚みを増大させる

  2018.10

  　

  　

  　View Summary

  幸野貴之，金野匠，小島隆，第98回 北海道医学大会・第51回北海道病理談話会：ワークショップ講演

• 子宮内膜腺癌細胞株の3次元培養下での3細胞間タイト結合タンパク質LSRの局在観察

  2017.09

  　

  　

  　View Summary

  幸野貴之，菊池真，金野匠，小島隆，第49回 日本臨床分子形態学会総会・学術集会：ワークショップ講演

• 3次元培養Sawano細胞でのLSRの細胞内局在

  2017.06

  　

  　

  　View Summary

  幸野貴之，金野匠，小島隆，第69回 日本細胞生物学会大会：ワークショップ講演

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Awards 【 display / non-display 】

Awards 【 display / non-display 】

• 秋山記念生命科学振興財団

  2022   研究助成（一般）  

• 第51回 日本臨床分子形態学会

  2019   優秀演題賞  

• 大和証券ヘルス財団

  2009   第36回調査研究助成  

• 秋山記念生命科学振興財団

  2008   研究助成（奨励）  

Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 癌細胞の休眠離脱を誘導する「隣接細胞間隙開裂型マクロ飲作用」の性状理解

  Project Year :

  2022.09

  -

  2023.03

   

  Authorship： Principal investigator

• タイト結合リガンドが呈した細胞間隙開裂型マクロ飲作用の機序理解と癌静穏化の新戦略

  基盤研究(C)

  Project Year :

  2022.04

  -

  2025.03

   

  幸野 貴之

• マクロ飲作用を利用した新しい癌悪性化抑制機序の開拓

  先端的研究

  Project Year :

  2020.07

  -

  2021.03

   

  幸野貴之

  Authorship： Principal investigator

• Analyses of malignant mechanisms via abnormality of novel multifunctional tricellular junction molecules in cancer cells

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

  -

  2022.03

   

  Kojima Takashi

  Authorship： Coinvestigator(s)

  　View Summary

  Multifunctional tricellular junction molecule angulin-1/LSR maintains the epithelial barrier and induces stability of the collecting cells. Its expression contributes to the malignancy of cancer cells via the binding effects with various functional molecules at tricellular contacts. We performed a multilateral analysis for the regulatory mechanisms and the roles LSR/ASPP2/PAR3/YAP complex proteins in normal human cells and cancer. As result, in various cancer cells, angulin-1/LSR is regulated via multiple intercellular signaling and prevents the malignancy.

• Analysis of the molecular mechanism of LSR ligand-dependent atypical macropinocytosis and following multilayered cell growth.

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2019.04

  -

  2022.03

   

  Kohno Takayuki

  Authorship： Principal investigator

  　View Summary

  Withdrawal from contact inhibition is necessary for epithelial cancer precursor cells to initiate cell growth and motility. Nevertheless, little is understood about the mechanism for the sudden initiation of cell growth under static conditions. We focused on cellular junctions as one region where breaking out of contact inhibition occurs. In well-differentiated endometrial cancer cells, the ligand administration for tricellular tight junction protein LSR, which transiently decreased the robust junction property, caused an abrupt increase in cell motility and consequent excessive multilayered cell growth despite being under contact inhibition conditions. We observed that macropinocytosis essentially and temporarily occurred as an antecedent event for the above process at intercellular junctions. We concluded that the formation of macropinocytosis, which is derived from tight junction-mediated signaling, was triggered for the initiation of cell growth in static precancerous epithelium.

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Presentations 【 display / non-display 】

Presentations 【 display / non-display 】

• 癌悪性化に付随する新しい細胞形態変化

  幸野貴之  [Invited]

  第123回 北海道癌談話会例会：特別講演 

  Presentation date： 2021.10

  Event date：

  2021.10

  　

  　

• 子宮内膜癌細胞で観察された，タイト結合刺激後の細胞間隙の一過性開裂現象と細胞機能への影響

  幸野貴之, 菊池真, 金野匠, 近藤昌夫, 郷久晴朗, 齋藤豪, 小島隆

  第51回日本臨床分子形態学会総会・学術集会：優秀演題賞 

  Presentation date： 2019.09

  Event date：

  2019.09

  　

  　

• Behavior of planar cell polarity and epithelial cell polarity in temperature-sensitive mouse cochlear precursor hair cells.

  Takuya Kakuki, Ryo Miyata, Ken-ichi Takano, Takayuki Kohno, Takafumi Ninomiya, Takumi Konno, Tetsuo Himi, Takashi Kojima

  EMBO / EMBL Symposium, Epithelia: The Building Blocks of Multicellularity 27-30 August 2014, Heidelberg, Germany 

• スフィンゴシン１-リン酸受容体Edg-1におけるアスパラギン結合糖鎖の役割．

  幸野貴之, 和田淳, 五靖十嵐之

  第53回 日本細胞生物学会：シンポジウム講演 

  Presentation date： 2000.10

• Bicellular and tricellular tight junction molecules localize to midbody and centrosome during cytokinesis in human endometrial carcinoma cell line.

  Takashi Kojima, Takumi Konno, Takayuki Kohno, Shin Kikuchi, Hiroshi Shimada, Seiro Satohisa, Tsuyoshi Saito

  ASCB / EMBO 2019 meeting 7-11 December 2019, Washington DC, US 

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Committee Memberships 【 display / non-display 】

Committee Memberships 【 display / non-display 】

• 2013.12

  -

  Now

    幹事