PAQR3 enhances Twist1 degradation to suppress epithelial-mesenchymal transition and metastasis of gastric cancer cells

Carcinogenesis
Weiwei GuoYan Chen

Abstract

Twist1 is an essential transcription factor required to initiate epithelial-mesenchymal transition (EMT) and promote tumor metastasis. PAQR3 is a newly found tumor suppressor that is frequently downregulated in many types of human cancers. Downregulation of PAQR3 is associated with accelerated metastasis and poor prognosis of the patients with gastric cancers. In this study, we demonstrate that PAQR3 is actively involved in the degradation of Twist1 and whereby regulates EMT and metastasis of gastric cancer cells. PAQR3 overexpression reduces the protein level but not the mRNA level of Twist1. The protein stability and polyubiquitination of Twist1 are altered by PAQR3. PAQR3 forms a complex with Twist1 and BTRC, an E3 ubiquitin ligase. PAQR3 enhances the interaction between Twist1 and BTRC. Twist1 is mobilized from the nucleus to a proteasome-containing structure in the cytoplasm upon overexpression of PAQR3 and BTRC, which is required for PAQR3-induced degradation of Twist1. The Twist1 box domain of the Twist1 protein is required for the interaction of Twist1 with both PAQR3 and BTRC, indispensable for PAQR3-mediated degradation of Twist1. Both BTRC and Twist1 are required for the inhibitory effects of PAQR3 on migration and E...Continue Reading

References

Mar 15, 1995·Genes & Development·Z F Chen, R R Behringer
Jun 17, 2005·Cancer Research·Wai Kei KwokXianghong Wang
Jul 27, 2005·Journal of Molecular Evolution·Y Tom TangWalter D Funk
Nov 25, 2005·British Journal of Cancer·A PuisieuxS Ansieau
Sep 27, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Terence K LeeSheung Tat Fan
May 18, 2007·Nature Reviews. Cancer·Héctor PeinadoAmparo Cano
Aug 29, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lin FengYan Chen
Feb 26, 2008·Nature Cell Biology·Muh-Hwa YangKou-Juey Wu
Apr 30, 2008·World Journal of Gastroenterology : WJG·Geng-Qiu LuoJian-Hua Zhou
Jun 13, 2008·The Biochemical Journal·Xiaolin LuoYan Chen
Jun 19, 2009·BMC Cell Biology·Shalini Singh, Anthony O Gramolini
Oct 7, 2009·Clinical & Experimental Metastasis·Mei-yan FengJing-shu Geng
Dec 23, 2009·Journal of Experimental & Clinical Cancer Research : CR·Ken SasakiTakashi Aikou
Dec 9, 2010·Cellular Signalling·Joyce PuttersGer J Strous
Jan 25, 2013·Nature Reviews. Cancer·Bram De Craene, Geert Berx
Jul 23, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Md Asaduzzaman KhanJunjiang Fu
Aug 29, 2013·Molecular Cancer Research : MCR·Rajendra P GajulaPhuoc T Tran
Feb 22, 2014·Nature Reviews. Molecular Cell Biology·Samy LamouilleRik Derynck
May 7, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Z Q LingY Chen
Jun 14, 2014·Proceedings of the National Academy of Sciences of the United States of America·Lei QiangYu-Ying He
Dec 17, 2014·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Zhiqiang MaJianyu Liu
May 20, 2015·Oncotarget·Abhisek MitraShulin Li
Jul 1, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·Z Q LingY Chen

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Citations

Jun 1, 2017·Oncology Reports·Chengcheng ZhaoRongping Zhou
May 22, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Shi-Lei TangWen-Zhong Hu

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