Rap2a is a novel target gene of p53 and regulates cancer cell migration and invasion

Cellular Signalling
Jin-Xia WuDong-Sheng Pei

Abstract

The p53 transcription factor is a critical regulator of the cell cycle, DNA repair, and apoptosis. Recent evidences suggest that p53 may contribute to the regulation of cell invasion and migration. Rap2a, a member of the small GTPase superfamily, mediates diverse cellular events such as cell adhesion, migration and proliferation through various signaling pathways. In this study, we identify that Rap2a is a novel target of p53 and is induced upon DNA damage in a p53-dependent manner. Upon DNA damage, p53 directly binds to the promoter of Rap2a and activates its transcription. We show that Rap2a is significantly upregulated in many types of tumors. In addition, the ectopic expression of Rap2a enhances the migration and invasive ability of cancer cells and increases activities of matrix metalloproteinase MMP2 and MMP9. In contrast, the inactivation of Rap2a inhibits cell invasion and activities of MMP2 and MMP9. We also show that Rap2a regulates the phosphorylation level of Akt. Collectively, our results show that ectopic expression of Rap2a has a key role in enhancing migration, invasion and metastasis by upregulating p-Akt.

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Citations

Mar 26, 2016·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhesi ZhuJunnian Zheng
Mar 30, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Jishu QuanMing Jin
Feb 2, 2019·PloS One·Shijie HeJeffrey J Fredberg
Feb 7, 2020·Journal of Ovarian Research·Zhengfang XiongLiyun Wang
Jul 2, 2020·Drug Design, Development and Therapy·Gao-Fei RenPeng-Fei Jiao
Apr 29, 2020·OncoTargets and Therapy·Xiucun WangZhengquan Yu
Feb 18, 2016·The Journal of Biological Chemistry·Saeideh Nakhaei-RadMohammad R Ahmadian
Dec 31, 2020·Journal of Cellular and Molecular Medicine·Ke-Jia WuChung-Hang Leung
May 22, 2021·Clinical and Experimental Medicine·Jing-Ru YangQuan-Lin Guan
Jun 7, 2021·Cellular & Molecular Biology Letters·Yanfen LianJiangtao Sun
Jul 9, 2021·Frontiers in Molecular Biosciences·Sarita KumariAnita Chopra

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