TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

Research output: Contribution to journalArticle


title = "TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p",
abstract = "Recent evidence suggests that the ion channel TRPA1 is implicated in lung adenocarcinoma (LUAD), where its role and mechanism of action remain unknown. We have previously established that the membrane receptor FGFR2 drives LUAD progression through aberrant protein-protein interactions mediated via its C-terminal proline-rich motif. Here we report that the N-terminal ankyrin repeats of TRPA1 directly bind to the C-terminal proline-rich motif of FGFR2 inducing the constitutive activation of the receptor, thereby prompting LUAD progression and metastasis. Furthermore, we show that upon metastasis to the brain, TRPA1 gets depleted, an effect triggered by the transfer of TRPA1-targeting exosomal microRNA (miRNA-142-3p) from brain astrocytes to cancer cells. This downregulation, in turn, inhibits TRPA1-mediated activation of FGFR2, hindering the metastatic process. Our study reveals a direct binding event and characterizes the role of TRPA1 ankyrin repeats in regulating FGFR2-driven oncogenic process; a mechanism that is hindered by miRNA-142-3p.",
author = "Jonathan Berrout and Eleni Kyriakopoulou and Lavanya Moparthi and Hogea, {Alexandra S.} and Liza Berrout and Cristina-Elena Ivan and Mihaela Lorger and Boyle, {John F.} and Chris Peers and Stephen Muench and Gomez, {Jacobo Elies} and Xin Hu and Carolyn Hurst and Thomas Hall and Sujanitha Umamaheswaran and Laura Wesley and Mihai Gagea and Michael Shires and Iain Manfield and Knowles, {Margaret A.} and Simon Davies and Klaus Suhling and Gonzalez, {Yurema Teijeiro} and Neil Carragher and Macleod, {Kenneth G.} and Abbott, {N Joan} and Calin, {George A} and Nikita Gamper and Zygmunt, {Peter M.} and Zahra Timsah",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41467-017-00983-w",
language = "English",
volume = "8",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",