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 】

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  THE JAPANESE CANCER ASSOCIATION

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  JAPAN SOCIETY FOR CELL BIOLOGY

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  THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

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 】

• The Roles and Regulatory Mechanisms of Tight Junction Protein Cingulin and Transcription Factor Forkhead Box Protein O1 in Human Lung Adenocarcinoma A549 Cells and Normal Lung Epithelial Cells

  Daichi Ishii, Yuma Shindo, Wataru Arai, Takumi Konno, Takayuki Kohno, Kazuya Honda, Masahiro Miyajima, Atsushi Watanabe, Takashi Kojima

  International Journal of Molecular Sciences    2024.01

  DOI

• The interplay between the epithelial permeability barrier, cell migration and mitochondrial metabolism of growth factors and their inhibitors in a human endometrial carcinoma cell line.

  Takumi Konno, Kohno T, Kikuchi S, Kura A, Saito K, Okada T, Shimada H, Yamazaki Y, Sugiyama T, Matsuura M, Ohsaki Y, Saito T, Kojima T

  Tissue barriers    2024.01

  　View Summary

  It is known that there are abnormalities of tight junction functions, cell migration and mitochondrial metabolism in human endometriosis and endometrial carcinoma. In this study, we investigated the effects of growth factors and their inhibitors on the epithelial permeability barrier, cell migration and mitochondrial metabolism in 2D and 2.5D cultures of human endometrioid endometrial carcinoma Sawano cells. We also investigated the changes of bicellular and tricellular tight junction molecules and ciliogenesis induced by these inhibitors. The growth factors TGF-β and EGF affected the epithelial permeability barrier, cell migration and expression of bicellular and tricellular tight junction molecules in 2D and 2.5D cultures of Sawano cells. EW-7197 (a TGF-β receptor inhibitor), AG1478 (an EGFR inhibitor) and SP600125 (a JNK inhibitor) affected the epithelial permeability barrier, cell migration and mitochondrial metabolism and prevented the changes induced by TGF-β and EGF in 2D and 2.5D cultures. EW-7197 and AG1478 induced ciliogenesis in 2.5D cultures. In conclusion, TGF-β and EGF promoted the malignancy of endometrial cancer via interplay among the epithelial permeability barrier, cell migration and mitochondrial metabolism. EW-7197 and AG1478 may be useful as novel therapeutic treatments options for endometrial cancer.

  DOI PubMed

• Oxygen–Glucose Deprivation Decreases the Motility and Length of Axonal Mitochondria in Cultured Dorsal Root Ganglion Cells of Rats

  Shin Kikuchi, Takayuki Kohno, Takashi Kojima, Haruyuki Tatsumi, Yuki Ohsaki, Takafumi Ninomiya

  Cellular and Molecular Neurobiology    2023.04  [Refereed]

  DOI

• Downregulation of angulin-1/LSR induces malignancy via upregulation of EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma A549 cells.

  Wataru Arai, Takumi Konno, Takayuki Kohno, Yuki Kodera, Mitsuhiro Tsujiwaki, Yuma Shindo, Hirofumi Chiba, Masahiro Miyajima, Yuji Sakuma, Atsushi Watanabe, Takashi Kojima

  Oncotarget   14   261 - 275  2023.03  [International journal]

  　View Summary

  Abnormal expression of bicellular tight junction claudins, including claudin-2 are observed during carcinogenesis in human lung adenocarcinoma. However, little is known about the role of tricellular tight junction molecule angulin-1/lipolysis-stimulated lipoprotein receptor (LSR). In the lung adenocarcinoma tissues examined in the present study, expression of claudin-2 was higher than in normal lung tissues, while angulin-1/LSR was poorly or faintly expressed. We investigated how loss of angulin-1/LSR affects the malignancy of lung adenocarcinoma cell line A549 and normal human lung epithelial (HLE) cells. The EGF receptor tyrosine kinase inhibitor AG1478 prevented the increase of claudin-2 expression induced by EGF in A549 cells. Knockdown of LSR induced expression of claudin-2 at the protein and mRNA levels and AG1478 prevented the upregulation of claudin-2 in A549 cells. Knockdown of LSR induced cell proliferation, cell migration and cell metabolism in A549 cells. Knockdown of claudin-2 inhibited the cell proliferation but did not affect the cell migration or cell metabolism of A549 cells. The TGF-β type I receptor inhibitor EW-7197 prevented the decrease of LSR and claudin-2 induced by TGF-β1 in A549 cells and 2D culture of normal HLE cells. EW-7197 prevented the increase of cell migration and cell metabolism induced by TGF-β1 in A549 cells. EW-7197 prevented the increase of epithelial permeability of FITC-4kD dextran induced by TGF-β1 in 2.5D culture of normal HLE cells. In conclusion, downregulation of angulin-1/LSR induces malignancy via EGF-dependent claudin-2 and TGF-β-dependent cell metabolism in human lung adenocarcinoma.

  DOI PubMed

• 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

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 子宮内膜悪性化におけるタイト結合分子claudin‐2の関与

  郷久晴朗, 嶋田浩志, 岩崎雅宏, 秋元太志, 西村庸子, 玉手雅人, 寺田倫子, 松浦基樹, 金野匠, 幸野貴之, 小島隆, 齋藤豪

  日本婦人科腫瘍学会雑誌 ( (公社)日本婦人科腫瘍学会 )  37 ( 3 ) 497 - 497  2019.06

  J-GLOBAL

• がん細胞の上皮バリアおよび悪性化における糖代謝の役割

  金野 匠, 幸野 貴之, 及能 大輔, 嶋田 浩志, 郷久 晴朗, 角木 拓也, 金子 躍人, 高野 賢一, 齋藤 豪, 小島 隆

  日本細胞生物学会大会講演要旨集 ( (一社)日本細胞生物学会 )  69回   95 - 95  2017.05

• 膵癌の悪性化における3細胞間タイト結合分子LSRの役割

  金野 匠, 及能 大輔, 河野 剛, 有元 千紘, 畠山 翔翼, 高橋 駿太, 幸野 貴之, 小島 隆

  日本病理学会会誌 ( (一社)日本病理学会 )  106 ( 1 ) 293 - 293  2017.03

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

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  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

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  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

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  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

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  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

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  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

  　

  　

• Staurosporine, a broad-range protein kinase inhibitor, induces elongation of actin filaments or microtubules as longer cellular protrusions.

  Kohno T, Ninomiya T, Kojima T

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

• Dynamic subcellular localization of LSR in Sawano cells

  Kohno T, Kikuchi S, Ninomiya T, Kojima T

  International Conference: Tight Junctions and their Proteins 8-10 September 2016, Berlin, Germany 

Committee Memberships 【 display / non-display 】

Committee Memberships 【 display / non-display 】

• 2013.12

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  Now

    幹事