2011 Fiscal Year Final Research Report
Stat3 targeted therapy in head and neck cancer
| Project/Area Number |
21592195
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Otorhinolaryngology
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| Research Institution | Kyushu University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SUZU Masum 名古屋市立大学, 教授 (30347158)
FUJII Masato 東京医療センター, 臨床研究センター (70129633)
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| Project Period (FY) |
2009 – 2011
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| Keywords | Stat3 / 分子標的 / CIN85 |
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| Research Abstract |
In head and neck squamous cell carcinoma(HNSCC), the frequent overexpression of EGFR is associated with the constitutive activation of Stat3. We analyzed the effects of Cbl interacting protein of 85 kDa(CIN85), which is involved in ligandinduced internalization of EGFR, focusing on EGFR signaling pathways. It was expected that CIN85 might exert inhibitory effects on EGFR signaling, thus leading to tumor inhibition. However, on the contrary, CIN85 was overexpressed in 40% of HNSCC tumor samples and this overexpression was significantly associated with advanced clinical stage. Mechanistic studies, in vitro, demonstrated that upon TGF-alpha stimuli, CIN85 activated MAPK cascade but inhibited Stat3 activity. Thus, it is suggested that in HNSCC, EGFR promotes carcinogenesis utilizing at least two different signaling axis : EGFR-CIN85-MAPK or EGFRStat3.
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