The cross-signaling of FGF receptor and integrin in cancer invasion and metastasis.
| Project/Area Number |
17K08775
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Morinomiya University of Medical Sciences |
|---|
Principal Investigator |
Mori Seiji 森ノ宮医療大学, 保健医療学部, 教授 (90467506)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
山本 浩文 大阪大学, 医学系研究科, 教授 (30322184)
河口 直正 森ノ宮医療大学, 保健医療学研究科, 教授 (70224748)
濱田 吉之輔 大阪大学, 医学系研究科, 特任准教授 (10362683)
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
|
|---|
| Keywords | インテグリン / 浸潤転移 / FGFR / FGF / EMT / がん / 癌 |
|---|
| Outline of Final Research Achievements |
Integrin and growth factor signaling is implicated in tumor progression. The effect of FGF family and integrin on tumor invasion and metastasis including epithelial-mesenchymal transition (EMT) have not been cleared yet. Previously, we have shown that FGF1 upregulates EMT depending on the binding FGF1 to integrin αvβ3. In this study, we focused the effect of FGF2 on tumor progression.
We found that FGF2 induced tumor cell migration and invasion but integrin-binding defective FGF2 mutant did not. Moreover, FGF2 mutant suppressed FGF signaling induced by wild-type FGF2. Furthermore, stimulation of FGF2 on mammary epithelial cells showed that the expression levels of EMT markers were upregulated by FGF2. Because FGF2 mutant did not show the effect, the binding of FGF2 and integrin αvβ3 is necessary for induction of EMT.
Our study suggests that interaction of integrin and FGF2 might be crucial for cancer progression, and FGF2 mutant has the potential to suppress cancer cell progression.
|
| Academic Significance and Societal Importance of the Research Achievements |
本研究は、増殖因子はそのレセプターのリガンドであり、細胞外基質はインテグリンのリガンドであるという既成の概念にとらわれず、増殖因子とインテグリンの相互作用という、新しいリガンドと受容体の関係を提示するものである。そして変異導入された増殖因子の抗腫瘍効果より、新規治療法の開発が期待される。FGFとインテグリンの間に存在する分子機構を詳細に解明することは、FGFとインテグリンの効果がとりわけ重要視されている癌の進展プロセス（浸潤・転移）の解明につながるものと考える。そして、このインテグリンと増殖因子レセプターのクロスシグナリングの解明が、今後、治療薬や診断法の開発に貢献するものと確信する。
|
Report
(4 results)
Research Products
(16 results)
-
[Journal Article] Mesothelial cells facilitate cancer stem-like properties in spheroids of ovarian cancer cells.2018
Author(s)
Shishido A, Mori S, Yokoyama Y, Hamada Y, Minami K, Qian Y, Wang J, Hirose H, Wu X, Kawaguchi N, Nagumo S, Matsuura N, Yamamoto H.
-
Journal Title
Oncol Rep
Volume: 4
Pages: 2105-2114
DOI
Related Report
Peer Reviewed / Open Access
-
[Journal Article] Overexpression of collagen type III in injured myocardium prevents cardiac systolic dysfunction by changing the balance of collagen distribution.2018
Author(s)
Uchinaka A, Yoshida M, Tanaka K, Hamada Y, Mori S, Maeno Y, Miyagawa S, Sawa Y, Nagata K, Yamamoto H, Kawaguchi N.
-
Journal Title
J Thorac Cardiovasc Sug.
Volume: 156
Issue: 1
Pages: 217-226
DOI
Related Report
Peer Reviewed
-
-
[Journal Article] The changes in metastatic potential of radioresistant cancer cell line generated by frequent X-ray.2017
Author(s)
Minami K, Hamada Y, Kawaguchi N, Mori S, Manabe M, Nakatani K, Tsubouchi K, Hayashi N, Yamamoto H, Koizumi M,
-
Journal Title
OHEM
Volume: E001
Pages: 1-12
Related Report
-
-
[Journal Article] X-ray and Carbon Ion Beam Irradiation Inhibited Angiogenesis via Integrin Up-regulation2017
Author(s)
Minami K, Hamada Y, Kawaguchi N, Mori S, Yokoyama Y, Oki Y, Adachi T, Kondo R, Shishido A, Matsushita Y, Usuki T, Manabe M, Koizumi M, Ogawa K, and Yamamoto H
-
Journal Title
Nano Biomed
Volume: 9
Pages: 94-104
NAID
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
-
-
