Molecular mechanism of tumor metastasis driven by cancer stem cells
| Project/Area Number |
17H03584
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Tumor biology
|
|---|
| Research Institution | Jikei University School of Medicine |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2017-04-01 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2019: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2017: ¥7,800,000 (Direct Cost: ¥6,000,000、Indirect Cost: ¥1,800,000)
|
|---|
| Keywords | 癌 / 幹細胞 / 転移 |
|---|
| Outline of Final Research Achievements |
Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of EMT is the key step for metastasis of cancer cells. We have recently demonstrated in breast cancer and ovarian serous adenocarcinoma that DYRK2 controls EMT. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We demonstrated that the ability of cell invasion and migration was abrogated in DYRK2-overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by an ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease-free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.
|
| Academic Significance and Societal Importance of the Research Achievements |
癌幹細胞は高い腫瘍形成能を持ち、転移や再発の原因になると考えられている。一方で多くの抗癌剤に耐性を示すことから、癌幹細胞を標的とした治療法の開発が切望されている。我々はすでにDYRK2が癌幹細胞の発生・維持制御分子であることを明らかにしており、本研究ではこの知見を腫瘍転移機構に発展させた。研究成果として大腸癌の肝転移モデルマウスを用いてDYRK2を発現させることで、酵素活性依存的に転移を抑制できることを示した。従ってDYRK2が転移抑制分子として臨床応用への展開が期待される。
|
Report
(4 results)
Research Products
(16 results)
-
-
-
[Journal Article] Forced expression of DYRK2 exerts anti-tumor effects via apoptotic induction in liver cancer.2019
Author(s)
Yokoyama-Mashima S, Yogosawa S, Kanegae Y, Hirooka S, Yoshida S, Horiuchi T, Ohashi T, Yanaga K, Saruta M, Oikawa T, Yoshida K.
-
Journal Title
Cancer Lett
Volume: 451
Pages: 100-109
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Journal Article] A Novel Near-infrared Fluorescent Protein, iRFP720, Facilitates Transcriptional Profiling of Prostate Cancer Bone Metastasis in Mice.2017
Author(s)
Honda M, Yogosawa S, Kamada M, Kamata Y, Kimura T, Koike Y, Harada T, Takahashi H, Egawa S, Yoshida K.
-
Journal Title
Anticancer Research
Volume: 37
Pages: 3009-3013
Related Report
Peer Reviewed
-
-
-
-
-
-
-
-
