The c-Jun NH2-terminal kinase 2 plays a dominant role in human epidermal neoplasia.

Journal Article (Journal Article)

The c-Jun NH(2)-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-kappaB. 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.

Full Text

Duke Authors

Cited Authors

  • Ke, H; Harris, R; Coloff, JL; Jin, JY; Leshin, B; Miliani de Marval, P; Tao, S; Rathmell, JC; Hall, RP; Zhang, JY

Published Date

  • April 15, 2010

Published In

Volume / Issue

  • 70 / 8

Start / End Page

  • 3080 - 3088

PubMed ID

  • 20354187

Pubmed Central ID

  • PMC2855785

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-09-2923


  • eng

Conference Location

  • United States