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

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TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. / Berrout, Jonathan; Kyriakopoulou, Eleni; Moparthi, Lavanya; Hogea, Alexandra S.; Berrout, Liza; Ivan, Cristina-Elena; Lorger, Mihaela; Boyle, John F.; Peers, Chris; Muench, Stephen; Gomez, Jacobo Elies; Hu, Xin; Hurst, Carolyn; Hall, Thomas; Umamaheswaran, Sujanitha; Wesley, Laura; Gagea, Mihai; Shires, Michael; Manfield, Iain; Knowles, Margaret A.; Davies, Simon; Suhling, Klaus; Gonzalez, Yurema Teijeiro; Carragher, Neil; Macleod, Kenneth G.; Abbott, N Joan; Calin, George A; Gamper, Nikita; Zygmunt, Peter M.; Timsah, Zahra.

In: Nature Communications, Vol. 8, No. 1, 983, 01.12.2017.

Research output: Contribution to journalArticle

Harvard

Berrout, J, Kyriakopoulou, E, Moparthi, L, Hogea, AS, Berrout, L, Ivan, C-E, Lorger, M, Boyle, JF, Peers, C, Muench, S, Gomez, JE, Hu, X, Hurst, C, Hall, T, Umamaheswaran, S, Wesley, L, Gagea, M, Shires, M, Manfield, I, Knowles, MA, Davies, S, Suhling, K, Gonzalez, YT, Carragher, N, Macleod, KG, Abbott, NJ, Calin, GA, Gamper, N, Zygmunt, PM & Timsah, Z 2017, 'TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p', Nature Communications, vol. 8, no. 1, 983. https://doi.org/10.1038/s41467-017-00983-w

APA

Berrout, J., Kyriakopoulou, E., Moparthi, L., Hogea, A. S., Berrout, L., Ivan, C-E., ... Timsah, Z. (2017). TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nature Communications, 8(1), [983]. https://doi.org/10.1038/s41467-017-00983-w

CBE

Berrout J, Kyriakopoulou E, Moparthi L, Hogea AS, Berrout L, Ivan C-E, Lorger M, Boyle JF, Peers C, Muench S, Gomez JE, Hu X, Hurst C, Hall T, Umamaheswaran S, Wesley L, Gagea M, Shires M, Manfield I, Knowles MA, Davies S, Suhling K, Gonzalez YT, Carragher N, Macleod KG, Abbott NJ, Calin GA, Gamper N, Zygmunt PM, Timsah Z. 2017. TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nature Communications. 8(1). https://doi.org/10.1038/s41467-017-00983-w

MLA

Vancouver

Berrout J, Kyriakopoulou E, Moparthi L, Hogea AS, Berrout L, Ivan C-E et al. TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. Nature Communications. 2017 Dec 1;8(1). 983. https://doi.org/10.1038/s41467-017-00983-w

Author

Berrout, Jonathan ; Kyriakopoulou, Eleni ; Moparthi, Lavanya ; Hogea, Alexandra S. ; Berrout, Liza ; Ivan, Cristina-Elena ; Lorger, Mihaela ; Boyle, John F. ; Peers, Chris ; Muench, Stephen ; Gomez, Jacobo Elies ; Hu, Xin ; Hurst, Carolyn ; Hall, Thomas ; Umamaheswaran, Sujanitha ; Wesley, Laura ; Gagea, Mihai ; Shires, Michael ; Manfield, Iain ; Knowles, Margaret A. ; Davies, Simon ; Suhling, Klaus ; Gonzalez, Yurema Teijeiro ; Carragher, Neil ; Macleod, Kenneth G. ; Abbott, N Joan ; Calin, George A ; Gamper, Nikita ; Zygmunt, Peter M. ; Timsah, Zahra. / TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p. In: Nature Communications. 2017 ; Vol. 8, No. 1.

RIS

TY - JOUR

T1 - TRPA1-FGFR2 binding event is a regulatory oncogenic driver modulated by miRNA-142-3p

AU - Berrout, Jonathan

AU - Kyriakopoulou, Eleni

AU - Moparthi, Lavanya

AU - Hogea, Alexandra S.

AU - Berrout, Liza

AU - Ivan, Cristina-Elena

AU - Lorger, Mihaela

AU - Boyle, John F.

AU - Peers, Chris

AU - Muench, Stephen

AU - Gomez, Jacobo Elies

AU - Hu, Xin

AU - Hurst, Carolyn

AU - Hall, Thomas

AU - Umamaheswaran, Sujanitha

AU - Wesley, Laura

AU - Gagea, Mihai

AU - Shires, Michael

AU - Manfield, Iain

AU - Knowles, Margaret A.

AU - Davies, Simon

AU - Suhling, Klaus

AU - Gonzalez, Yurema Teijeiro

AU - Carragher, Neil

AU - Macleod, Kenneth G.

AU - Abbott, N Joan

AU - Calin, George A

AU - Gamper, Nikita

AU - Zygmunt, Peter M.

AU - Timsah, Zahra

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-017-00983-w

DO - 10.1038/s41467-017-00983-w

M3 - Article

VL - 8

JO - Nature Communications

T2 - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 983

ER -