2011 Fiscal Year Final Research Report
Role of TWEAK-Fn14 signaling under high-fat diet or obesity on prostate cancer progression
| Project/Area Number |
22791464
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Urology
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| Research Institution | Akita University |
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Principal Investigator |
HUANG Mingguo 秋田大学, 大学院・医学系研究科, 助教 (60448503)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 腫瘍学 |
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| Research Abstract |
In Japan, prostate cancer (Pca) morbidity and mortality have been increasing, presumably due to changes in dietary habits, higher rates of screening and an expanding elderly population. Recent studies shown that high-fat diet (HFD) active PI3K and MAPK by the modulate many important growth factors including IGF-1, FGF and EGF in prostate cancer (Kalaany NY et al, Nature, 2009).
Recently we demonstrated HFD influence progression of prostate cancer, and found that many receptors of growth factors and cytokine implicated progression of prostate cancer in the prostate cancer xenograft (Narita S et al, Prostate, 2008)。
In this study, we investigated the role of Fn14 on prostate-cancer progression using prostate cancer cells, LNCaP prostate cancer xenograft model and human prostate cancer samples. Fn14 and its ligand TWEAK were highly expressed in the androgen independent prostate cancer cells, and Fn14 was shown to modulate expression of matrix metalloproteinase-9 (MMP-9), and influence the proliferation and invasiveness of prostate cancer cells. Clinically, high expression of Fn14 was significantly associated with higher PSA recurrence rate in patients who underwent radical prostatectomy.
In conclusion, the over expression of Fn14 may contribute to multiple malignant cellular phenotypes associated with prostate cancer progression, in part via MMP-9. TWEAK-Fn14 signaling may be a novel therapeutic target of prostate cancer.
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Research Products
(4 results)
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[Journal Article] Overexpression of Fn14 promotes androgen-independent prostate cancer progression through MMP-9 and correlates with poor treatment outcome2011
Author(s)
Mingguo Huang, Shintaro Narita, Norihiko Tsuchiya, Zhiyong Ma, Kazuyuki Numakura, Takashi Obara, Hiroshi Tsuruta, Mitsuru Saito, Takamitsu Inoue, Yohei Horikawa, Shigeru Satoh and Tomonori Habuchi
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Journal Title
Carcinogenesis
Volume: 32(11)
Pages: 1589-96
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