Disruption of c-Jun reduces cellular migration and invasion through inhibition of c-Src and hyperactivation of ROCK II kinase.

Authors

Xuanmao Jiao, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Sanjay Katiyar, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Manran Liu, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Susette C Mueller, Georgetown University, Lombardi Comprehensive Cancer Center
Michael P. Lisanti, Thomas Jefferson UniversityFollow
Anping Li, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Timothy G Pestell, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Kongming Wu, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Xiaoming Ju, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Zhiping Li, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Erwin F Wagner, Spanish Cancer Research Center (CNIO)Follow
Tatsuo Takeya, Graduate School of Biological Sciences, Nara Institute of Science and Technology
Chenguang Wang, Kimmel Cancer Center, Thomas Jefferson UniversityFollow
Richard G Pestell, Kimmel Cancer Center, Thomas Jefferson UniversityFollow

Document Type

Article

Publication Date

4-1-2008

Comments

This article has been peer reviewed and is published in Molecular Biology of the Cell 2008, 19(4): 1378-1390. The published version is available at DOI: 10.1091/mbc.E07-08-0753. ©The American Society for Cell Biology

Abstract

The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding member of the activator protein-1 family and is required for cellular proliferation and DNA synthesis in response to oncogenic signals and plays an essential role in chemical carcinogenesis. The role of c-Jun in cellular invasion remains to be defined. Genetic deletion of c-Jun in transgenic mice is embryonic lethal; therefore, transgenic mice encoding a c-Jun gene flanked by LoxP sites (c-jun(f/f)) were used. c-jun gene deletion reduced c-Src expression, hyperactivated ROCK II signaling, and reduced cellular polarity, migration, and invasiveness. c-Jun increased c-Src mRNA abundance and c-Src promoter activity involving an AP-1 site in the c-Src promoter. Transduction of c-jun(-/-) cells with either c-Jun or c-Src retroviral expression systems restored the defective cellular migration of c-jun(-/-) cells. As c-Src is a critical component of pathways regulating proliferation, survival, and metastasis, the induction of c-Src abundance, by c-Jun, provides a novel mechanism of cooperative signaling in cellular invasion.

Recommended Citation

Jiao, Xuanmao; Katiyar, Sanjay; Liu, Manran; Mueller, Susette C; Lisanti, Michael P.; Li, Anping; Pestell, Timothy G; Wu, Kongming; Ju, Xiaoming; Li, Zhiping; Wagner, Erwin F; Takeya, Tatsuo; Wang, Chenguang; and Pestell, Richard G, "Disruption of c-Jun reduces cellular migration and invasion through inhibition of c-Src and hyperactivation of ROCK II kinase." (2008). Kimmel Cancer Center Faculty Papers. Paper 13.
https://jdc.jefferson.edu/kimmelccfp/13

PubMed ID

18216279