CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells

Abstract We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis an...

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Autores principales:	Daniel Wicklein, Benjamin Otto, Anna Suling, Eva Elies, Georg Lüers, Tobias Lange, Susanne Feldhaus, Hanna Maar, Jennifer Schröder-Schwarz, Georg Brunner, Christoph Wagener, Udo Schumacher
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/18afeaf98aab49c89e5e0549bf4f9baf
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spelling	oai:doaj.org-article:18afeaf98aab49c89e5e0549bf4f9baf2021-12-02T15:09:01ZCEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells10.1038/s41598-018-30338-42045-2322https://doaj.org/article/18afeaf98aab49c89e5e0549bf4f9baf2018-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-30338-4https://doaj.org/toc/2045-2322Abstract We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metastasis was quantified histologically. Results and identified markers were verified using tissue samples of over 100 melanoma patients. Knockdown of CEACAM1 prolonged the animals’ survival by significantly reducing subcutaneous growth of MeWo tumors and spontaneous lung metastasis. Microarray analysis revealed a strong influence of CEACAM1 knockdown on the network of EMT associated genes in the xenograft tumors (e.g. downregulation of BRAF, FOSL1, NRAS and TWIST). IGFBP7 and Latexin (highest up- and downregulated expression in microarray analysis) were found to be associated with longer and shorter survival, respectively, of melanoma patients. High FOSL1 and altered TWIST1 expression were found to be correlated with shortened survival in the cohort of melanoma patients. After a stepwise selection procedure combining above markers, multivariate analysis revealed IGFBP7, Latexin and altered TWIST to be prognostic markers for death. CEACAM1 could be a target for melanoma therapy as an alternative to (or in combination with) immune checkpoint and BRAF inhibitors.Daniel WickleinBenjamin OttoAnna SulingEva EliesGeorg LüersTobias LangeSusanne FeldhausHanna MaarJennifer Schröder-SchwarzGeorg BrunnerChristoph WagenerUdo SchumacherNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel Wicklein Benjamin Otto Anna Suling Eva Elies Georg Lüers Tobias Lange Susanne Feldhaus Hanna Maar Jennifer Schröder-Schwarz Georg Brunner Christoph Wagener Udo Schumacher CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
description	Abstract We investigated the functional role of CEACAM1 in a spontaneous metastasis xenograft model of human melanoma in scid mice using BRAF wildtype MeWo cells with and without RNAi mediated knockdown of CEACAM1. Tumors from the xenograft model were subjected to whole genome expression analysis and metastasis was quantified histologically. Results and identified markers were verified using tissue samples of over 100 melanoma patients. Knockdown of CEACAM1 prolonged the animals’ survival by significantly reducing subcutaneous growth of MeWo tumors and spontaneous lung metastasis. Microarray analysis revealed a strong influence of CEACAM1 knockdown on the network of EMT associated genes in the xenograft tumors (e.g. downregulation of BRAF, FOSL1, NRAS and TWIST). IGFBP7 and Latexin (highest up- and downregulated expression in microarray analysis) were found to be associated with longer and shorter survival, respectively, of melanoma patients. High FOSL1 and altered TWIST1 expression were found to be correlated with shortened survival in the cohort of melanoma patients. After a stepwise selection procedure combining above markers, multivariate analysis revealed IGFBP7, Latexin and altered TWIST to be prognostic markers for death. CEACAM1 could be a target for melanoma therapy as an alternative to (or in combination with) immune checkpoint and BRAF inhibitors.
format	article
author	Daniel Wicklein Benjamin Otto Anna Suling Eva Elies Georg Lüers Tobias Lange Susanne Feldhaus Hanna Maar Jennifer Schröder-Schwarz Georg Brunner Christoph Wagener Udo Schumacher
author_facet	Daniel Wicklein Benjamin Otto Anna Suling Eva Elies Georg Lüers Tobias Lange Susanne Feldhaus Hanna Maar Jennifer Schröder-Schwarz Georg Brunner Christoph Wagener Udo Schumacher
author_sort	Daniel Wicklein
title	CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
title_short	CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
title_full	CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
title_fullStr	CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
title_full_unstemmed	CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells
title_sort	ceacam1 promotes melanoma metastasis and is involved in the regulation of the emt associated gene network in melanoma cells
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/18afeaf98aab49c89e5e0549bf4f9baf
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CEACAM1 promotes melanoma metastasis and is involved in the regulation of the EMT associated gene network in melanoma cells

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