| Item type |
文献 / Documents(1) |
| 公開日 |
2022-10-31 |
| アクセス権 |
|
|
アクセス権 |
open access |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.1111/cas.15567 |
|
|
関連名称 |
10.1111/cas.15567 |
| 出版タイプ |
|
|
出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
|
|
タイトル |
TIMP1 Promotes Cell Proliferation and Invasion Capability of Right-sided Colon Cancers via the FAK/Akt Signaling Pathway |
| タイトル別表記 |
|
|
その他のタイトル |
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 |
| 著者 |
馬, 貝貝
上田, 浩之
岡本, 耕一
板東, 正浩
フジモト, ショウタ
岡田, 泰行
川口, 智之
ワダ, ヒロノリ
宮本, 弘志
島田, 光生
佐藤, 康史
高山, 哲治
|
| 抄録 |
|
|
内容記述 |
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. |
| キーワード |
|
|
主題 |
TIMP1 |
| キーワード |
|
|
主題 |
Colorectal cancer |
| キーワード |
|
|
主題 |
Tumor location |
| キーワード |
|
|
主題 |
Prognosis |
| キーワード |
|
|
主題 |
Organoids |
| 書誌情報 |
en : Cancer Science
発行日 2022-09-08
|
| 収録物ID |
|
|
収録物識別子タイプ |
ISSN |
|
収録物識別子 |
13497006 |
| 出版者 |
|
|
出版者 |
Japanese Cancer Association |
| 出版者 |
|
|
出版者 |
John Wiley & Sons |
| 備考 |
|
|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Beibei Maの学位論文として提出され，学位審査・授与の対象となっている。
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| EID |
|
|
識別子 |
392530 |
| 言語 |
|
|
言語 |
eng |
| 報告番号 |
|
|
学位授与番号 |
甲第3660号 |
| 学位記番号 |
|
|
値 |
甲医第1542号 |
| 学位授与年月日 |
|
|
学位授与年月日 |
2022-09-22 |
| 学位名 |
|
|
学位名 |
博士（医学） |
| 学位授与機関 |
|
|
|
学位授与機関名 |
徳島大学 |
k3660_abstract.pdf (129 KB)
.png)
