TY - JOUR A1 - Kreis, Nina-Naomi A1 - Friemel, Alexandra A1 - Ritter, Andreas Hans A1 - Roth, Susanne A1 - Rolle, Udo A1 - Louwen, Frank A1 - Yuan, Juping T1 - Function of p21 (Cip1/Waf1/CDKN1A) in migration and invasion of cancer and trophoblastic cells T2 - Cancers N2 - 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. KW - p21 KW - CDKN1A KW - trophoblastic cell lines KW - invasion KW - ERK3/MAPK6 KW - MMP2 KW - TIMP2 Y1 - 2019 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/51264 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-512646 SN - 2072-6694 N1 - 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 VL - 11 IS - 7, Art. 989 SP - 1 EP - 17 PB - MDPI CY - Basel ER -