PLK1/vimentin signaling facilitates immune escape by recruiting Smad2/3 to PD-L1 promoter in metastatic lung adenocarcinoma.

Cell Death and Differentiation
Hay-Ran JangHyungshin Yim

Abstract

The prerequisite function of vimentin for the epithelial-mesenchymal transition (EMT) is not clearly elucidated yet. Here, we show that vimentin phosphorylated by PLK1, triggers TGF-β-signaling, which consequently leads to metastasis and PD-L1 expression for immune suppression in lung adenocarcinoma. The clinical correlation between expression of both vimentin and PLK1, and overall survival rates of patients was significant in lung adenocarcinoma but not in squamous cell carcinoma. The phosphorylation of vimentin was accompanied by the activation of PLK1 during TGF-β-induced EMT in lung adenocarcinoma. Among the several phosphorylation sites determined by phospho-proteomic analysis and the site-specific mutagenesis, the phosphorylation at S339 displayed the most effective metastasis and tumourigenesis with the highest expression of PD-L1, compared with that of wild-type and other versions in both 3D cell culture and tail-vein injection metastasis models. Phosphomimetic vimentin at S339 interacted with p-Smad2 for its nuclear localization, leading to the expression of PD-L1. Clinical relevance revealed the inverse correlation between the survival rates of patients and the expressions of VIM, PLK1, and CD274 in primary and metast...Continue Reading

References

Jan 1, 1994·Annual Review of Biochemistry·E Fuchs, K Weber
Aug 1, 1996·The Journal of Cell Biology·R D GoldmanP M Steinert
Sep 10, 2002·Proceedings of the National Academy of Sciences of the United States of America·Yoshiko IwaiNagahiro Minato
Nov 2, 2005·The Journal of Cell Biology·Tomoya YamaguchiMasaki Inagaki
Apr 5, 2007·Nature Protocols·Joel D NelsonKarol Bomsztyk
Dec 7, 2007·Cancer Research·Aylin RizkiMina J Bissell
May 9, 2009·Journal of Molecular Biology·Markus MeierPeter Burkhard
Jan 26, 2010·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Melissa G MendezRobert D Goldman
Dec 15, 2010·Seminars in Cancer Biology·Tsukasa Shibue, Robert A Weinberg
May 4, 2011·International Journal of Cancer. Journal International Du Cancer·Jose T ThaiparambilAdam I Marcus
Jun 4, 2011·Cellular and Molecular Life Sciences : CMLS·Arun Satelli, Shulin Li
Oct 18, 2011·Cell·Scott Valastyan, Robert A Weinberg
Mar 23, 2012·Nature Reviews. Cancer·Drew M Pardoll
Sep 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Gang XiaoXiaolong Liu
Oct 26, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Xiaofeng JiangF Stephen Hodi
Dec 18, 2012·Oncoimmunology·Laurence Zitvogel, Guido Kroemer
Jan 29, 2013·Journal of Cancer Research and Clinical Oncology·Nami YamashitaYoshihiko Maehara
Apr 23, 2013·Oncogene·H Zheng, Y Kang
Dec 19, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Martin GregorGerhard Wiche
Mar 19, 2014·Mutation Research. Reviews in Mutation Research·Hyungshin Yim, Raymond L Erikson
Mar 11, 2015·Therapeutic Advances in Medical Oncology·Raghav SundarRoss A Soo
Jun 3, 2015·Nature Communications·Dolores Pérez-SalaF Javier Cañada
Jul 10, 2016·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Masaki ShimojiTetsuya Mitsudomi
Sep 25, 2016·The Journal of Biological Chemistry·Jia LiDale D Tang
Mar 25, 2017·Expert Opinion on Biological Therapy·Johan VansteenkisteAlexander Spira
Jun 22, 2017·The New England Journal of Medicine·David P CarboneUNKNOWN CheckMate 026 Investigators
Oct 3, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Imran Khan, Patricia S Steeg
Dec 7, 2017·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Alessandra M RichardsonAdam I Marcus
Jan 27, 2018·Cell Death & Disease·Tatiana V DenisenkoBoris Zhivotovsky

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