Noncanonical activation of receptor tyrosine kinases: next target mechanisms for cancer progression
| Project/Area Number |
16H04694
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Tumor biology
|
|---|
| Research Institution | University of Toyama |
|---|
Principal Investigator |
Hiroaki Sakurai 富山大学, 大学院医学薬学研究部(薬学), 教授 (00345571)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
小澤 龍彦 富山大学, 大学院医学薬学研究部(医学), 助教 (10432105)
|
|---|
| Co-Investigator(Renkei-kenkyūsha) |
Yuki Kawasaki 富山大学, 大学院医学薬学研究部(薬学), 助教 (30432107)
|
|---|
| Project Period (FY) |
2016-04-01 – 2019-03-31
|
| Project Status |
Completed (Fiscal Year 2018)
|
| Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
|
|---|
| Keywords | がん / シグナル伝達 / チロシンキナーゼ / リン酸化 / 小胞輸送 / EGFR / EphA2 / 受容体 / 増殖因子 / キナーゼ / 細胞 / 癌 |
|---|
| Outline of Final Research Achievements |
Receptor tyrosine kinases are involved in cancer progression, and are main target molecules for the development of anti-cancer agents. In this study, we tried to elucidate new mechanisms of their activation by focusing on non-canonical activation. We found that EGFR, an oncogene of lung and colorectal cancers, is regulated by two different mechanisms. One is classically known ligand-bound receptor and the other is ligand-unbound receptor monomers. Especially, the unligande EGFR monomers are endocytosed and then recycled back to the plasma membrane. We also characterized the role of EphA2 receptor in cancer cell migration and found that EphA2 is localized to migrating front via Rab11-containing recycling endosome.
|
| Academic Significance and Societal Importance of the Research Achievements |
チロシンキナーゼ型受容体を標的とした、がん分子標的治療が大きく進展している。しかし、その活性化機構には、従来知られている古典的なものに加えて、我々は新しい調節機構の存在を明らかにしている。今回、肺がんや大腸がんの治療標的分子であるEGFRにおいて、二つの目の活性化機構が存在することを見出した。したがって、その活性化機構を標的とした新しい治療戦略の構築に道を拓く研究成果を得ることができた。
|
Report
(4 results)
Research Products
(32 results)
-
-
-
-
-
-
-
-
[Journal Article] Feedback control of ErbB2 via ERK-mediated phosphorylation of a conserved threonine in the juxtamembrane domain2016
Author(s)
Kawasaki Y, Sakimura A, Park CM, Tomaru R, Tanaka T, Ozawa T, Zhou Y, Narita K, Kishi H, Muraguchi A, Sakurai H
-
Journal Title
Sci Rep
Volume: 6
Issue: 1
Pages: 31502-31502
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Crucial roles of RSK in cell motility by catalyzing Ser-897 phosphorylation of EphA2.2016
Author(s)
Zhou Y, Yamada N, Tanaka T, Hori T, Yokoyama S, Hayakawa Y, Yano S, Fukuoka J, Koizumi K, Saiki I, Sakurai H．
Organizer
The 16th Biennial Congress of the Metastasis Research Society
Place of Presentation
China
Year and Date
2016-09-15
Related Report
Int'l Joint Research
-
-
