Ras-induced invasion and metastasis are regulated by a leukotriene B4 receptor BLT2-linked pathway

Oncogene
E-Y KimJ-H Kim

Abstract

Ras signaling pathways are well-recognized for their involvement in cancer cell proliferation; however, considerably less is known regarding their contribution to invasion and metastasis. Here, we demonstrate that a novel BLT2, a low-affinity leukotriene B(4) receptor-linked signaling cascade involving the generation of reactive oxygen species (ROS) via Nox1, NF-kappaB stimulation and subsequent upregulation of matrix metalloproteinase-9 (MMP-9) is a potential mechanism by which Ras promotes invasion and metastasis. We found that inhibition of BLT2 signaling markedly suppressed Ras-evoked metastasis and reduced the associated mortality in mice. Consistent with the proposed role of BLT2 as a key downstream mediator of Ras signaling to metastasis, BLT2 expression alone resulted in the formation of numerous metastatic lung nodules and the nodules formation was significantly attenuated by the inhibition of MMP-9, a downstream component of BLT2. Together, our results reveal the previously unsuspected function of BLT2-linked cascade in driving oncogenic Ras-induced metastasis and would provide a valuable insight into invasion and metastasis.

References

May 20, 1996·Biochimica Et Biophysica Acta·C BortuzzoB Rigas
Oct 1, 1995·Journal of Lipid Mediators and Cell Signalling·T YokomizoT Shimizu
Mar 30, 2001·The Journal of Biological Chemistry·T YokomizoT Shimizu
Jan 5, 2002·The Journal of Biological Chemistry·Chang-Hoon WooJae-Hong Kim
Mar 20, 2002·The Journal of Biological Chemistry·Kotha SubbaramaiahAndrew J Dannenberg
Jun 28, 2002·Cancer Metastasis Reviews·D NieK V Honn
Jul 10, 2002·Nature Cell Biology·Martin OftAllan Balmain
Jan 2, 2003·Nature Reviews. Cancer·Julian Downward
Nov 5, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mario Romano, Joan Claria
Dec 4, 2003·Biochemical Society Transactions·L BehrendR M Zwacka
Mar 17, 2004·Seminars in Cancer Biology·Paul M Campbell, Channing J Der
Oct 19, 2004·Oncogene·Min-Hyuk YooJae-Hong Kim
Jan 22, 2005·Carcinogenesis·Rafael MayoralPaloma Martín-Sanz
Feb 1, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Anna ZampetakiQingbo Xu
Apr 22, 2005·Biological Chemistry·Klaudia Giehl
Apr 23, 2005·Anti-cancer Drugs·Xian-Zhong DingThomas E Adrian
May 4, 2005·Cancer Research·Achim KrügerRafael Fridman
May 24, 2005·Biochimica Et Biophysica Acta·Mikael Björklund, Erkki Koivunen
Jun 22, 2005·Neoplasia : an International Journal for Oncology Research·Rene HennigThomas E Adrian
Jul 8, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Zezong GuStuart A Lipton
Jul 22, 2005·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Johanna NikkolaSeppo Pyrhönen
Dec 29, 2005·International Journal of Cancer. Journal International Du Cancer·R Daniel BonfilRafael Fridman
Apr 21, 2006·Proceedings of the National Academy of Sciences of the United States of America·Hong QiuJesper Z Haeggström
May 9, 2006·Cancer Metastasis Reviews·Elena I Deryugina, James P Quigley
Aug 8, 2006·Biochemical and Biophysical Research Communications·Eun Ha ShinYoe-Sik Bae
Nov 15, 2006·Annual Review of Medicine·Yong I Cha, Raymond N DuBois
Dec 13, 2006·Cancer Metastasis Reviews·Wen-Sheng Wu
Jul 7, 2007·Sub-cellular Biochemistry·Randall E Harris
Sep 4, 2007·Cancer Metastasis Reviews·Man-Tzu WangDaotai Nie
Sep 4, 2007·TheScientificWorldJournal·Thomas G Brock, Marc Peters-Golden
Dec 18, 2007·Free Radical Biology & Medicine·Jung-A ChoiJae-Hong Kim
Apr 19, 2008·Reproductive Sciences·Rodney P RocconiWarner K Huh
Mar 17, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Geun-Young KimJae-Hong Kim

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Citations

Jun 26, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Dragana NikitovicGeorge Tzanakakis
Oct 7, 2011·Cell Death & Disease·D R Gough, T G Cotter
Aug 25, 2012·Nature Reviews. Cancer·Karen Block, Yves Gorin
Jan 22, 2011·Experimental & Molecular Medicine·Ji Min SeoJae Hong Kim
Mar 20, 2012·Biochemical and Biophysical Research Communications·Jin-Wook LeeJae-Hong Kim
Jan 27, 2017·International Journal of Molecular Sciences·Gillian Y Moore, Graham P Pidgeon
Jan 1, 2011·Cancers·Marino VeneritoPeter Malfertheiner
Jun 18, 2020·Antioxidants·Mong-Heng WangMohamed Al-Shabrawey
Jul 5, 2018·Cancer Metastasis Reviews·Wanyeon KimBuHyun Youn
Oct 23, 2020·Circulation Journal : Official Journal of the Japanese Circulation Society·Xiaoxi YangTetsushi Furukawa
Jan 17, 2021·International Journal of Molecular Sciences·Francesca BerettiTullia Maraldi
Feb 28, 2021·Signal Transduction and Targeted Therapy·Bei WangDao Wen Wang
Jul 25, 2021·Cancers·Elisabetta SautaValentina Sancisi

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