Oncotarget

Research Papers:

Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways

Gang Li, Li Ying, Hong Wang, Si-Si Wei, Jie Chen, Yi-He Chen, Wei-Ping Xu, Qi-Qiang Jie, Qing Zhou, Yi-Gang Li, Yi-Dong Wei and Yue-Peng Wang _

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Oncotarget. 2016; 7:17970-17985. https://doi.org/10.18632/oncotarget.7602

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Abstract

Gang Li1,4,*, Li Ying2,*, Hong Wang1, Si-Si Wei3, Jie Chen1, Yi-He Chen1, Wei-Ping Xu1, Qi-Qiang Jie4, Qing Zhou1, Yi-Gang Li1, Yi-Dong Wei4 and Yue-Peng Wang1

1 Department of Cardiology, Affiliated Xinhua Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China

2 Department of Neurology, Affiliated Xinhua Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China

3 Department of Pediatrics, Affiliated Xinhua Hospital, Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai, China

4 Department of Cardiology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, China

* These authors have contributed equally to this work

Correspondence to:

Yue-Peng Wang, email:

Yi-Dong Wei, email:

Yi-Gang Li, email:

Keywords: Rac1b, cell proliferation, apoptosis, JNK2, AKT2

Received: October 19, 2015 Accepted: February 13, 2016 Published: February 22, 2016

Abstract

Rac1b is a constitutively activated, alternatively spliced form of the small GTPase Rac1. Previous studies showed that Rac1b promotes cell proliferation and inhibits apoptosis. In the present study, we used microarray analysis to detect genes differentially expressed in HEK293T cells and SW480 human colon cancer cells stably overexpressing Rac1b. We found that the pro-proliferation genes JNK2, c-JUN and cyclin-D1 as well as anti-apoptotic AKT2 and MCL1 were all upregulated in both lines. Rac1b promoted cell proliferation and inhibited apoptosis by activating the JNK2/c-JUN/cyclin-D1 and AKT2/MCL1 pathways, respectively. Very low Rac1b levels were detected in the colonic epithelium of wild-type Sprague-Dawley rats. Knockout of the rat Rac1 gene exon-3b or knockdown of endogenous Rac1b in HT29 human colon cancer cells downregulated only the AKT2/MCL1 pathway. Our study revealed that very low levels of endogenous Rac1b inhibit apoptosis, while Rac1b upregulation both promotes cell proliferation and inhibits apoptosis. It is likely the AKT2/MCL1 pathway is more sensitive to Rac1b regulation.


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