TIMP1 Promotes Cell Proliferation and Invasion Capability of Right-sided Colon Cancers via the FAK/Akt Signaling Pathway

• Material Type: 博士論文
• Title: TIMP1 Promotes Cell Proliferation and Invasion Capability of Right-sided Colon Cancers via the FAK/Akt Signaling Pathway
• Author/Editor: Ma, Beibei; Ueda, Hiroyuki; Okamoto, Koichi; Bando, Masahiro; Fujimoto, Shota; Okada, Yasuyuki; Kawaguchi, Tomoyuki; Wada, Hironori; Miyamoto, Hiroshi; Shimada, Mitsuo; Sato, Yasushi; Takayama, Tetsuji
• Author Heading: Ma, Beibei; Ueda, Hiroyuki; Okamoto, Koichi; Bando, Masahiro; Fujimoto, Shota; Okada, Yasuyuki; Kawaguchi, Tomoyuki; Wada, Hironori; Miyamoto, Hiroshi; Shimada, Mitsuo; Sato, Yasushi; Takayama, Tetsuji
• Publication, Distribution, etc.: Japanese Cancer Association|John Wiley & Sons
• Publication Date: 2022-09-08
• Publication Date (W3CDTF): 2022-09-08
• Alternative Title: 右側大腸癌ではTIMP1がFAK/Aktシグナル経路を介して細胞増殖活性及び浸潤能を促進する
• Periodical title: Cancer Science
• ISSN (Periodical Title): ISSN : 1349-7006
• Degree grantor/type: 徳島大学
• Date Granted: 2022-09-22
• Dissertation Number: 甲第3660号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: TIMP1; Colorectal cancer; Tumor location; Prognosis; Organoids
• Target Audience: 一般
• Note (General): Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis. Cell proliferation activity and invasion capability in right-sided cancer PDOs were significantly higher than in left-sided cancer PDOs and normal PDOs, as revealed by Cell Titer Glo and transwell assays, respectively. We then used quantitative RT-PCR to compare 184 genes in 30 pathways among right-sided and left-sided cancer and normal PDOs and found that the TIMP1 mRNA level was highest in right-sided PDOs. TIMP1 protein levels were upregulated in right-sided PDOs compared with normal PDOs but was downregulated in left-sided PDOs. TIMP1 knockdown with shRNA significantly decreased cell proliferation activity and invasion capability in right-sided PDOs but not in left-sided PDOs. Moreover, TIMP1 knockdown significantly decreased pFAK and pAkt expression levels in right-sided PDOs but not in left-sided PDOs. A database analysis of The Cancer Genome Atlas revealed that TIMP1 expression in right-sided CRCs was significantly higher than in left-sided CRCs. Kaplan–Meier survival analysis showed significantly shorter overall survival in high-TIMP1 patients versus low-TIMP1 patients with right-sided CRCs but not left-sided CRCs. Our data suggest that TIMP1 is overexpressed in right-sided CRCs and promotes cell proliferation and invasion capability through the TIMP1/FAK/Akt pathway, leading to a poor prognosis. The TIMP1/FAK/Akt pathway can be a target for therapeutic agents in right-sided CRCs.
• Format (IMT): application/pdf
• Access Restrictions: インターネット公開
• Rights (production): This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
• Related Material (DOI): 10.1111/cas.15567
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/117615/20221020170709611039/k3660_abstract.pdf fulltext

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