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 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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Author:Nina-Naomi KreisORCiDGND, Alexandra Friemel, Andreas Ritter, Susanne Roth, Udo RolleORCiDGND, Frank LouwenGND, Juping Yuan
Pubmed Id:
Parent Title (English):Cancers
Place of publication:Basel
Document Type:Article
Year of Completion:2019
Date of first Publication:2019/07/15
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2019/09/30
Tag:CDKN1A; ERK3/MAPK6; MMP2; TIMP2; invasion; p21; trophoblastic cell lines
Issue:7, Art. 989
Page Number:17
First Page:1
Last Page:17
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0