Journal
ONCOTARGET
Volume 7, Issue 14, Pages 17970-17985Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.7602
Keywords
Rac1b; cell proliferation; apoptosis; JNK2; AKT2; MCL1
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Funding
- Welcome Trust for New Principal Investigators of Xinhua Hospital
- Pujiang Project for Extraordinary Scientist of the Science and Technology Commission of Shanghai Municipality [12PJ1406400]
- Natural Science Foundation of Zhejiang Province [Y2101019]
- Natural Science Foundation of China (NSFC) [81170302, 81270258, 81270193, 30800466, 81370257, 81470497, 81530015]
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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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