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Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells

Tumor progression and pregnancy have several features in common. Tumor cells and placental trophoblasts share many signaling pathways involved in migration and invasion. Preeclampsia, associated with impaired differentiation and migration of trophoblastic cells, is an unpredictable and unpreventable...

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Autores principales: Kreis, Nina-Naomi, Friemel, Alexandra, Ritter, Andreas, Roth, Susanne, Rolle, Udo, Louwen, Frank, Yuan, Juping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678555/
https://www.ncbi.nlm.nih.gov/pubmed/31311187
http://dx.doi.org/10.3390/cancers11070989
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author Kreis, Nina-Naomi
Friemel, Alexandra
Ritter, Andreas
Roth, Susanne
Rolle, Udo
Louwen, Frank
Yuan, Juping
author_facet Kreis, Nina-Naomi
Friemel, Alexandra
Ritter, Andreas
Roth, Susanne
Rolle, Udo
Louwen, Frank
Yuan, Juping
author_sort Kreis, Nina-Naomi
collection PubMed
description Tumor progression and pregnancy have several features in common. Tumor cells and placental trophoblasts share many signaling pathways involved in migration and invasion. Preeclampsia, associated with impaired differentiation and migration of trophoblastic cells, is an unpredictable and unpreventable disease leading to maternal and perinatal mortality and morbidity. Like in tumor cells, most pathways, in which p21 is involved, are deregulated in trophoblasts of preeclamptic placentas. The aim of the present study was to enlighten p21’s role in tumorigenic choriocarcinoma and trophoblastic cell lines. We show that knockdown of p21 induces defects in chromosome movement during mitosis, though hardly affecting proliferation and cell cycle distribution. Moreover, suppression of p21 compromises the migration and invasion capability of various trophoblastic and cancer cell lines mediated by, at least partially, a reduction of the extracellular signal-regulated kinase 3, identified using transcriptome-wide profiling, real-time PCR, and Western blot. Further analyses show that downregulation of p21 is associated with reduced matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2. This work evinces that p21 is involved in chromosome movement during mitosis as well as in the motility and invasion capacity of trophoblastic and cancer cell lines.
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spelling pubmed-66785552019-08-19 Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells Kreis, Nina-Naomi Friemel, Alexandra Ritter, Andreas Roth, Susanne Rolle, Udo Louwen, Frank Yuan, Juping Cancers (Basel) Article Tumor progression and pregnancy have several features in common. Tumor cells and placental trophoblasts share many signaling pathways involved in migration and invasion. Preeclampsia, associated with impaired differentiation and migration of trophoblastic cells, is an unpredictable and unpreventable disease leading to maternal and perinatal mortality and morbidity. Like in tumor cells, most pathways, in which p21 is involved, are deregulated in trophoblasts of preeclamptic placentas. The aim of the present study was to enlighten p21’s role in tumorigenic choriocarcinoma and trophoblastic cell lines. We show that knockdown of p21 induces defects in chromosome movement during mitosis, though hardly affecting proliferation and cell cycle distribution. Moreover, suppression of p21 compromises the migration and invasion capability of various trophoblastic and cancer cell lines mediated by, at least partially, a reduction of the extracellular signal-regulated kinase 3, identified using transcriptome-wide profiling, real-time PCR, and Western blot. Further analyses show that downregulation of p21 is associated with reduced matrix metalloproteinase 2 and tissue inhibitor of metalloproteinases 2. This work evinces that p21 is involved in chromosome movement during mitosis as well as in the motility and invasion capacity of trophoblastic and cancer cell lines. MDPI 2019-07-15 /pmc/articles/PMC6678555/ /pubmed/31311187 http://dx.doi.org/10.3390/cancers11070989 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kreis, Nina-Naomi
Friemel, Alexandra
Ritter, Andreas
Roth, Susanne
Rolle, Udo
Louwen, Frank
Yuan, Juping
Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells
title Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells
title_full Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells
title_fullStr Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells
title_full_unstemmed Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells
title_short Function of p21 (Cip1/Waf1/CDKN1A) in Migration and Invasion of Cancer and Trophoblastic Cells
title_sort function of p21 (cip1/waf1/cdkn1a) in migration and invasion of cancer and trophoblastic cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678555/
https://www.ncbi.nlm.nih.gov/pubmed/31311187
http://dx.doi.org/10.3390/cancers11070989
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