Roles of LSR in cancer metabolic reprogramming and cell adhesion
| Project/Area Number |
20K16196
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49020:Human pathology-related
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
Takasawa Kumi 札幌医科大学, 医学部, 助教 (50359709)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | LSR / タイト結合 / 細胞接着 / がん代謝 / 子宮頸がん / がん / cell adhesion |
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| Outline of Research at the Start |
本研究では、脂質代謝と細胞間接着という二つの細胞機能を併せ持つユニークなLSRという分子に着目して、がん細胞の代謝経路の包括的な変動（代謝リプログラミング）と細胞間接着の密接な関わりの解明を目指す。得られる知見は、LSRにとどまらず、タイト結合関連タンパク質ががんで異常発現する意義の再構築につながる。さらに、脂質代謝選択的な新たな治療戦略の創出、抗LSR抗体療法の効果機序の解明に寄与する。制がん研究において重要な役割を担いつつある代謝リプログラミングの理解に異なる視点を与え、新たな治療戦略創出に寄与するものである。
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| Outline of Final Research Achievements |
Immunohistochemistry with anti-LSR antibodies was performed on surgical material of cervical adenocarcinoma and its staining pattern was evaluated. The results showed a significant difference in the expression of LSR in each cancer component compared to non-neoplastic cervical glandular epithelium and breast duct epithelium. LSR expression-deficient lines generated by the CRISPR-Cas9 system had significantly reduced various tumor malignant potentials compared to control cell lines. Comparative proteomic analysis detected several gene ontology (GO) terms related to cell adhesion. In addition, LSR expression analysis of multiple breast cancer cell lines confirmed that LSR expression was increased by treatment with a couple of drugs.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでに、子宮頸がんにおけるLSRの異所性高発現および子宮頸がん悪性化におけるLSRの役割解明に関する研究は皆無である。細胞膜表面に異所性高発現するLSRは診断マーカーとして有望であると同時に、分子標的治療のターゲットともなり得ることから、本研究で得られる知見は、分子機序の理解に役立つと共に、LSR高発現がんの治療戦略立案にも寄与すると期待される。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Aberrant expression of junctional adhesion molecule-A contributes to the malignancy of cervical adenocarcinoma by interaction with poliovirus receptor/CD155.2021
Author(s)
Murakami T, Takasawa A, Takasawa K, Akimoto T, Aoyama T, Magara K, Saito Y, Ota M, Kyuno D, Yamamoto S, Hasegawa T, Saito T, Osanai M.
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Journal Title
Cancer Science
Volume: 112
Issue: 2
Pages: 906-917
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A systemic apolipoprotein A-IV-associated amyloidosis confirmed by proteome analysis.2021
Author(s)
Murakami T, Takasawa A, Moriki A, Igaki Y, Ikeda H, Murase K, Takada K, Magara K, Aoyama T, Ono Y, Kyuno D, Takasawa K, Murata M, Osanai M.
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Journal Title
Virchows Archiv
Volume: in press
Related Report
Peer Reviewed
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[Journal Article] Aldolase A promotes epithelial-mesenchymal transition to increase malignant potentials of cervical adenocarcinoma.2020
Author(s)
Saito Y, Takasawa A, Takasawa K, Aoyama T, Akimoto T, Ota M, Magara K, Murata M, Hirohashi H, Hasegawa T, Sawada N, Saito T, Osanai M.
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Journal Title
Cancer Science
Volume: 111
Issue: 8
Pages: 3071-3081
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Abberant high expression of ALDOA contributes to the malignant transformation of uterine cervical adenocarcinoma2021
Author(s)
Akira Takasawa, Yuki Saito, Kumi Takasawa, Taishi Akimoto, Kazufumi Magara, Tomoyuki Aoyama, Yusuke Ono, Daisuke Kyuno, Yoshihiko Hirohashi, Tsuyoshi Saito, Makoto Osanai.
Organizer
The 39th Sapporo International Cancer Symposium
Related Report
Int'l Joint Research
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