| Item Type |
Article |
| ID |
|
| Preview |
| Image |
|
| Caption |
|
|
| Full text |
KAKEN_17H01401seika.pdf
| Type |
:application/pdf |
Download
|
| Size |
:591.2 KB
|
| Last updated |
:Nov 14, 2022 |
| Downloads |
: 583 |
Total downloads since Nov 14, 2022 : 583
|
|
| Release Date |
|
| Title |
| Title |
転写調節因子MKL1によるがん関連線維芽細胞誘導機構の解明とがん治療への応用
|
| Kana |
テンシャ チョウセツ インシ MKL1 ニ ヨル ガン カンレン センイガ サイボウ ユウドウ キコウ ノ カイメイ ト ガン チリョウ エノ オウヨウ
|
| Romanization |
Tensha chōsetsu inshi MKL1 ni yoru gan kanren sen'iga saibō yūdō kikō no kaimei to gan chiryō eno ōyō
|
|
| Other Title |
| Title |
Elucidation of underlyingmechanism of MKL1-mediated induction of cancer associated fibroblasts and its clinical applications
|
| Kana |
|
| Romanization |
|
|
| Creator |
| Name |
佐谷, 秀行
 |
| Kana |
サヤ, ヒデユキ
|
| Romanization |
Saya, Hideyuki
|
| Affiliation |
慶應義塾大学・医学部 (信濃町) ・教授
|
| Affiliation (Translated) |
|
| Role |
Research team head
|
| Link |
科研費研究者番号 : 80264282
|
| Name |
信末, 博行
|
| Kana |
ノブスエ, ヒロユキ
|
| Romanization |
Nobusue, Hiroyuki
|
| Affiliation |
慶應義塾大学・医学部 (信濃町) ・特任助教
|
| Affiliation (Translated) |
|
| Role |
Research team member
|
| Link |
科研費研究者番号 : 90525685
|
|
| Edition |
|
| Place |
|
| Publisher |
|
| Date |
| Issued (from:yyyy) |
2020
|
| Issued (to:yyyy) |
|
| Created (yyyy-mm-dd) |
|
| Updated (yyyy-mm-dd) |
|
| Captured (yyyy-mm-dd) |
|
|
| Physical description |
|
| Source Title |
| Name |
科学研究費補助金研究成果報告書
|
| Name (Translated) |
|
| Volume |
|
| Issue |
|
| Year |
2019
|
| Month |
|
| Start page |
|
| End page |
|
|
| ISSN |
|
| ISBN |
|
| DOI |
|
| URI |
|
| JaLCDOI |
|
| NII Article ID |
|
| Ichushi ID |
|
| Other ID |
|
| Doctoral dissertation |
| Dissertation Number |
|
| Date of granted |
|
| Degree name |
|
| Degree grantor |
|
|
| Abstract |
種々の間質細胞 (線維芽細胞、間葉系前駆細胞および脂肪細胞) を骨肉腫細胞の培養上清で処理するとMKL1が活性化し、がん関連線維芽細胞 (CAFs) への転換が誘導された。種々の間質細胞にMKL1の発現を惹起すると、CAF関連遺伝子の発現が増加し、CAFの特徴を獲得した。また、転写因子のSRFとの結合が、MKL1誘導によるCAF分化に必要であることも分かった。さらに、ROCK阻害剤のFasudilはアクチンの動態変化を介してMKL1を負に制御すること、またin vivoにおいてCAF分化を阻害し骨肉腫形成を抑制することを見出した。以上から、MKL1がCAF分化の主たる制御分子であることが分かった。
In various stromal cells (fibroblasts, mesenchymal progenitor cells, and adipocytes), conditioned medium obtained from cultured osteosarcoma cells enhanced the activation of megakaryoblastic leukemia 1 (MKL1) which is a transcriptional regulator as well as induced the transition of these cells to cancer-associated fibroblasts (CAFs). We induced expression of MKL1 in various stromal cells and found that they increased expression of CAF-related genes and acquired CAF phenotypes. We also found that the interaction with serum response factor (SRF) is required for MKL1-induced CAF differentiation. In addition, we found that Rho-kinase inhibitor fasudil prevented nuclear translocation of MKL1 via actin dynamics and suppressed CAF differentiation as well as tumor formation in mouse osteosarcoma model. These findings suggest that MKL1 is a master regulator of the transition of stromal cells to CAFs and blocking CAF differentiation may provide a novel therapeutic approach for cancers.
|
|
| Table of contents |
|
| Keyword |
|
| NDC |
|
| Note |
研究種目 : 基盤研究 (A) (一般)
研究期間 : 2017～2019
課題番号 : 17H01401
研究分野 : 腫瘍生物学
|
|
| Language |
|
| Type of resource |
|
| Genre |
|
| Text version |
|
| Related DOI |
|
| Access conditions |
|
| Last modified date |
|
| Creation date |
|
| Registerd by |
|
| History |
| Mar 5, 2021 | | インデックス を変更 |
| Nov 14, 2022 | | Creator Name,Creator Kana,Creator Romanization,Creator Affiliation,Creator Affiliation (Translated),Creator Role,Creator Link,Abstract 内容,Note 注記 を変更 |
|
|
| Index |
|
| Related to |
|
