The role of ASPP2/LSR/AMOT/Merlin/YAP-protein complex at tricellular contacts of normal and cancer cells
| Project/Area Number |
16K11146
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小島 隆 札幌医科大学, 医学部, 教授 (30260764)
斉藤 豪 札幌医科大学, 医学部, 教授 (90145566)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 子宮内膜癌 / 正常子宮内膜上皮細胞 / ASPP2 / 悪性化 / Hippo pathway / TEAD1/AREG / LSR / YAP / 正常培養ヒト子宮内膜上皮細胞 / PAR3 / ヒストン脱アセチル化酵素阻害剤 / AMOT/Merlin / 婦人科腫瘍学 |
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| Outline of Final Research Achievements |
In the present study, we found the role and the regulatory mechanisms of ASPP2/LSR/AMOT/Merlin/YAP-protein complex in the malignancy of cancer cells. In human endometrial cancer tissues, LSR and ASPP2 downregulated during the malignancy. In human endometrial cancer cell line, downregulation of LSR promoted cell migration and cell invasion via transcriptional factor TEAD1/AREG. The mechanisms may be two pathways: 1) the Hippo pathway and 2) YAP/AMOT pathway.
Downregulation of ASPP2 decreased LSR, increased phosphorylation of YAP and enhanced cell migration and cell invasion. In normal human epithelial cells derived from the surgery, expression, distribution and regulation of both LSR and ASPP2 were almost similar. Taken together, ASPP2/LSR/AMOT/Merlin/YAP-protein complex are formed at tricellular contacts and they may prevent the malignancy of endometrial cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究のASPP2/LSR/AMOT/Merlin/YAP蛋白複合体の正常および癌細胞における役割の解明は、今までにない新しいアプローチであり、今まで解明されていなかった脂質代謝と正常上皮バリアおよび癌の悪性化の関係も明らかになる。最終的には、ASPP2/LSR/AMOT/Merlin/YAP蛋白複合体をターゲットとした癌の悪性化の予防および分子標的治療にも繋がり社会的意義は大きいと考えられる。
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Report
(4 results)
Research Products
(22 results)
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[Journal Article] Loss of tricellular tight junction protein LSR promotes cell invasion and migration via upregulation of TEAD1/AREG in human endometrial cancer.2017
Author(s)
Shimada H, Abe S, Kohno K, Satohisa S, Konno T, Takahashi S, Hatakeyama T, Arimoto C, Kakuki T, Kaneko Y, Takano K, Saito T, Kojima T
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Journal Title
Sci Rep.
Volume: 7
Issue: 1
Pages: 10935-10935
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The role of claudin-2 on the malignancy of human endometrioid carcinoma2018
Author(s)
Seiro Satohisa, Hiroshi Shimada, Takayuki Kohno, Takumi Konno, Masato Tamate, Motoki Matsuura, Mizue Teramoto, Taishi Akimoto, Masahiro Iwasaki, Takashi Kojima, Tsuyoshi Saito
Organizer
ESGO Sate of the Art Conference 2018
Related Report
Int'l Joint Research
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[Presentation] Loss of ASPP2 promotes cell invasion and migration via YAP in human endometrial cancer2018
Author(s)
Hiroshi Shimada, Seiro Satohisa, T. Konno, M. Matsuura, M. Teramoto, T. Kohno, M. Iwasaki, T. Kojima, T. Saito
Organizer
IGCS 17th Biennial Meeting of the International Gynecologic Cancer Society（September.13-16, 2018, Kyoto, Japan)
Related Report
Int'l Joint Research
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