NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells

Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchan...
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Autor*in:	Keller, Maureen [verfasserIn] Dubois, Fatéméh Teulier, Sylvain Martin, Alexandre P. J. Levallet, Jérôme Maille, Elodie Brosseau, Solenn Elie, Nicolas Hergovich, Alexander Bergot, Emmanuel Camonis, Jacques Zalcman, Gérard Levallet, Guénaëlle

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2019

Schlagwörter:	RASSF1A GEF-H1 YAP NDR2 kinase Lung cancer

Anmerkung:	© The Author(s). 2019

Übergeordnetes Werk:	Enthalten in: Journal of experimental & clinical cancer research - Berlin : Springer, 2008, 38(2019), 1 vom: 12. Apr.
Übergeordnetes Werk:	volume:38 ; year:2019 ; number:1 ; day:12 ; month:04

Links:	Volltext

DOI / URN:	10.1186/s13046-019-1145-8

Katalog-ID:	SPR029646324

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520			\|a Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects.
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700	1		\|a Dubois, Fatéméh \|4 aut
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allfields	10.1186/s13046-019-1145-8 doi (DE-627)SPR029646324 (SPR)s13046-019-1145-8-e DE-627 ger DE-627 rakwb eng Keller, Maureen verfasserin aut NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. RASSF1A (dpeaa)DE-He213 GEF-H1 (dpeaa)DE-He213 YAP (dpeaa)DE-He213 NDR2 kinase (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Dubois, Fatéméh aut Teulier, Sylvain aut Martin, Alexandre P. J. aut Levallet, Jérôme aut Maille, Elodie aut Brosseau, Solenn aut Elie, Nicolas aut Hergovich, Alexander aut Bergot, Emmanuel aut Camonis, Jacques aut Zalcman, Gérard aut Levallet, Guénaëlle aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 12. Apr. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:12 month:04 https://dx.doi.org/10.1186/s13046-019-1145-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 38 2019 1 12 04
spelling	10.1186/s13046-019-1145-8 doi (DE-627)SPR029646324 (SPR)s13046-019-1145-8-e DE-627 ger DE-627 rakwb eng Keller, Maureen verfasserin aut NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. RASSF1A (dpeaa)DE-He213 GEF-H1 (dpeaa)DE-He213 YAP (dpeaa)DE-He213 NDR2 kinase (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Dubois, Fatéméh aut Teulier, Sylvain aut Martin, Alexandre P. J. aut Levallet, Jérôme aut Maille, Elodie aut Brosseau, Solenn aut Elie, Nicolas aut Hergovich, Alexander aut Bergot, Emmanuel aut Camonis, Jacques aut Zalcman, Gérard aut Levallet, Guénaëlle aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 12. Apr. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:12 month:04 https://dx.doi.org/10.1186/s13046-019-1145-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 38 2019 1 12 04
allfields_unstemmed	10.1186/s13046-019-1145-8 doi (DE-627)SPR029646324 (SPR)s13046-019-1145-8-e DE-627 ger DE-627 rakwb eng Keller, Maureen verfasserin aut NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. RASSF1A (dpeaa)DE-He213 GEF-H1 (dpeaa)DE-He213 YAP (dpeaa)DE-He213 NDR2 kinase (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Dubois, Fatéméh aut Teulier, Sylvain aut Martin, Alexandre P. J. aut Levallet, Jérôme aut Maille, Elodie aut Brosseau, Solenn aut Elie, Nicolas aut Hergovich, Alexander aut Bergot, Emmanuel aut Camonis, Jacques aut Zalcman, Gérard aut Levallet, Guénaëlle aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 12. Apr. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:12 month:04 https://dx.doi.org/10.1186/s13046-019-1145-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 38 2019 1 12 04
allfieldsGer	10.1186/s13046-019-1145-8 doi (DE-627)SPR029646324 (SPR)s13046-019-1145-8-e DE-627 ger DE-627 rakwb eng Keller, Maureen verfasserin aut NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. RASSF1A (dpeaa)DE-He213 GEF-H1 (dpeaa)DE-He213 YAP (dpeaa)DE-He213 NDR2 kinase (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Dubois, Fatéméh aut Teulier, Sylvain aut Martin, Alexandre P. J. aut Levallet, Jérôme aut Maille, Elodie aut Brosseau, Solenn aut Elie, Nicolas aut Hergovich, Alexander aut Bergot, Emmanuel aut Camonis, Jacques aut Zalcman, Gérard aut Levallet, Guénaëlle aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 12. Apr. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:12 month:04 https://dx.doi.org/10.1186/s13046-019-1145-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 38 2019 1 12 04
allfieldsSound	10.1186/s13046-019-1145-8 doi (DE-627)SPR029646324 (SPR)s13046-019-1145-8-e DE-627 ger DE-627 rakwb eng Keller, Maureen verfasserin aut NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells 2019 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2019 Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. RASSF1A (dpeaa)DE-He213 GEF-H1 (dpeaa)DE-He213 YAP (dpeaa)DE-He213 NDR2 kinase (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213 Dubois, Fatéméh aut Teulier, Sylvain aut Martin, Alexandre P. J. aut Levallet, Jérôme aut Maille, Elodie aut Brosseau, Solenn aut Elie, Nicolas aut Hergovich, Alexander aut Bergot, Emmanuel aut Camonis, Jacques aut Zalcman, Gérard aut Levallet, Guénaëlle aut Enthalten in Journal of experimental & clinical cancer research Berlin : Springer, 2008 38(2019), 1 vom: 12. Apr. (DE-627)568921380 (DE-600)2430698-8 1756-9966 nnns volume:38 year:2019 number:1 day:12 month:04 https://dx.doi.org/10.1186/s13046-019-1145-8 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 38 2019 1 12 04
language	English
source	Enthalten in Journal of experimental & clinical cancer research 38(2019), 1 vom: 12. Apr. volume:38 year:2019 number:1 day:12 month:04
sourceStr	Enthalten in Journal of experimental & clinical cancer research 38(2019), 1 vom: 12. Apr. volume:38 year:2019 number:1 day:12 month:04
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	RASSF1A GEF-H1 YAP NDR2 kinase Lung cancer
isfreeaccess_bool	true
container_title	Journal of experimental & clinical cancer research
authorswithroles_txt_mv	Keller, Maureen @@aut@@ Dubois, Fatéméh @@aut@@ Teulier, Sylvain @@aut@@ Martin, Alexandre P. J. @@aut@@ Levallet, Jérôme @@aut@@ Maille, Elodie @@aut@@ Brosseau, Solenn @@aut@@ Elie, Nicolas @@aut@@ Hergovich, Alexander @@aut@@ Bergot, Emmanuel @@aut@@ Camonis, Jacques @@aut@@ Zalcman, Gérard @@aut@@ Levallet, Guénaëlle @@aut@@
publishDateDaySort_date	2019-04-12T00:00:00Z
hierarchy_top_id	568921380
id	SPR029646324
language_de	englisch
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author	Keller, Maureen
spellingShingle	Keller, Maureen misc RASSF1A misc GEF-H1 misc YAP misc NDR2 kinase misc Lung cancer NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells
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topic_title	NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells RASSF1A (dpeaa)DE-He213 GEF-H1 (dpeaa)DE-He213 YAP (dpeaa)DE-He213 NDR2 kinase (dpeaa)DE-He213 Lung cancer (dpeaa)DE-He213
topic	misc RASSF1A misc GEF-H1 misc YAP misc NDR2 kinase misc Lung cancer
topic_unstemmed	misc RASSF1A misc GEF-H1 misc YAP misc NDR2 kinase misc Lung cancer
topic_browse	misc RASSF1A misc GEF-H1 misc YAP misc NDR2 kinase misc Lung cancer
format_facet	Elektronische Aufsätze Aufsätze Elektronische Ressource
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hierarchy_parent_title	Journal of experimental & clinical cancer research
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title	NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells
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title_full	NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells
author_sort	Keller, Maureen
journal	Journal of experimental & clinical cancer research
journalStr	Journal of experimental & clinical cancer research
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author_browse	Keller, Maureen Dubois, Fatéméh Teulier, Sylvain Martin, Alexandre P. J. Levallet, Jérôme Maille, Elodie Brosseau, Solenn Elie, Nicolas Hergovich, Alexander Bergot, Emmanuel Camonis, Jacques Zalcman, Gérard Levallet, Guénaëlle
container_volume	38
format_se	Elektronische Aufsätze
author-letter	Keller, Maureen
doi_str_mv	10.1186/s13046-019-1145-8
title_sort	ndr2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of rassf1a tumor-suppressor gene in lung cancer cells
title_auth	NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells
abstract	Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. © The Author(s). 2019
abstractGer	Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. © The Author(s). 2019
abstract_unstemmed	Background RASSF1A, a tumor suppressor gene, is frequently inactivated in lung cancer leading to a YAP-dependent epithelial-mesenchymal transition (EMT). Such effects are partly due to the inactivation of the anti-migratory RhoB GTPase via the inhibitory phosphorylation of GEF-H1, the GDP/GTP exchange factor for RhoB. However, the kinase responsible for RhoB/GEF-H1 inactivation in RASSF1A-depleted cells remained unknown. Methods NDR1/2 inactivation by siRNA or shRNA effects on epithelial-mesenchymal transition, invasion, xenograft formation and growth in SCID−/− Beige mice, apoptosis, proliferation, cytokinesis, YAP/TAZ activation were investigated upon RASSF1A loss in human bronchial epithelial cells (HBEC). Results We demonstrate here that depletion of the YAP-kinases NDR1/2 reverts migration and metastatic properties upon RASSF1A loss in HBEC. We show that NDR2 interacts directly with GEF-H1 (which contains the NDR phosphorylation consensus motif HXRXXS/T), leading to GEF-H1 phosphorylation. We further report that the RASSF1A/NDR2/GEF-H1/RhoB/YAP axis is involved in proper cytokinesis in human bronchial cells, since chromosome proper segregation are NDR-dependent upon RASSF1A or GEF-H1 loss in HBEC. Conclusion To summarize, our data support a model in which, upon RASSF1A silencing, NDR2 gets activated, phosphorylates and inactivates GEF-H1, leading to RhoB inactivation. This cascade induced by RASSF1A loss in bronchial cells is responsible for metastasis properties, YAP activation and cytokinesis defects. © The Author(s). 2019
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container_issue	1
title_short	NDR2 kinase contributes to cell invasion and cytokinesis defects induced by the inactivation of RASSF1A tumor-suppressor gene in lung cancer cells
url	https://dx.doi.org/10.1186/s13046-019-1145-8
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author2	Dubois, Fatéméh Teulier, Sylvain Martin, Alexandre P. J. Levallet, Jérôme Maille, Elodie Brosseau, Solenn Elie, Nicolas Hergovich, Alexander Bergot, Emmanuel Camonis, Jacques Zalcman, Gérard Levallet, Guénaëlle
author2Str	Dubois, Fatéméh Teulier, Sylvain Martin, Alexandre P. J. Levallet, Jérôme Maille, Elodie Brosseau, Solenn Elie, Nicolas Hergovich, Alexander Bergot, Emmanuel Camonis, Jacques Zalcman, Gérard Levallet, Guénaëlle
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up_date	2024-07-04T01:51:00.082Z
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