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- Hengning Ke
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Rebecca Harris
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Jonathan L. Coloff
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Jane Y. Jin
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Benjamin Leshin
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Paula Miliani de Marval
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Shiying Tao
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Jeffrey C. Rathmell
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Russell P. Hall
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
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- Jennifer Y. Zhang
- Authors' Affiliations: Departments of 1Dermatology and 2Pharmacology and Cancer Biology, Duke University, Durham, North Carolina and 3Department of Dermatology, Stanford University, Stanford, California
説明
<jats:title>Abstract</jats:title> <jats:p>The c-Jun NH2-terminal kinase (JNK) signaling cascade has been implicated in a wide range of diseases, including cancer. It is unclear how different JNK proteins contribute to human cancer. Here, we report that JNK2 is activated in more than 70% of human squamous cell carcinoma (SCC) samples and that inhibition of JNK2 pharmacologically or genetically impairs tumorigenesis of human SCC cells. Most importantly, JNK2, but not JNK1, is sufficient to couple with oncogenic Ras to transform primary human epidermal cells into malignancy with features of SCC. JNK2 prevents Ras-induced cell senescence and growth arrest by reducing the expression levels of the cell cycle inhibitor p16 and the activation of NF-κB. On the other hand, JNK, along with phosphoinositide 3-kinase, is essential for Ras-induced glycolysis, an energy-producing process known to benefit cancer growth. These data indicate that JNK2 collaborates with other oncogenes, such as Ras, at multiple molecular levels to promote tumorigenesis and hence represents a promising therapeutic target for cancer. Cancer Res; 70(8); 3080–8. ©2010 AACR.</jats:p>
収録刊行物
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- Cancer Research
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Cancer Research 70 (8), 3080-3088, 2010-04-14
American Association for Cancer Research (AACR)
