TY  - JOUR
A1  - Kreis, Nina-Naomi
A1  - Louwen, Frank
A1  - Zimmer, Brigitte
A1  - Yuan, Juping
T1  - Loss of p21Cip1/CDKN1A renders cancer cells susceptible to Polo-like kinase 1 inhibition
T2  - Oncotarget
N2  - The deregulation of Polo-like kinase 1 is inversely linked to the prognosis of patients with diverse human tumors. Targeting Polo-like kinase 1 has been widely considered as one of the most promising strategies for molecular anticancer therapy. While the preclinical results are encouraging, the clinical outcomes are rather less inspiring by showing limited anticancer activity. It is thus of importance to identify molecules and mechanisms responsible for the sensitivity of Polo-like kinase 1 inhibition. We have recently shown that p21Cip1/CDKN1A is involved in the regulation of mitosis and its loss prolongs the mitotic duration accompanied by defects in chromosome segregation and cytokinesis in various tumor cells. In the present study, we demonstrate that p21 affects the efficacy of Polo-like kinase 1 inhibitors, especially Poloxin, a specific inhibitor of the unique Polo-box domain. Intriguingly, upon treatment with Polo-like kinase 1 inhibitors, p21 is increased in the cytoplasm, associated with anti-apoptosis, DNA repair and cell survival. By contrast, deficiency of p21 renders tumor cells more susceptible to Polo-like kinase 1 inhibition by showing a pronounced mitotic arrest, DNA damage and apoptosis. Furthermore, long-term treatment with Plk1 inhibitors induced fiercely the senescent state of tumor cells with functional p21. We suggest that the p21 status may be a useful biomarker for predicting the efficacy of Plk1 inhibition.
KW  - p21
KW  - Plk1 inhibitors
KW  - apoptosis
KW  - DNA damage
KW  - senescence
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/37365
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-373658
UR  - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=2844
SN  - 1949-2553
N1  - This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
VL  - 6
IS  - 9
SP  - 6611
EP  - 6626
PB  - Impact Journals LLC
CY  - [S.l.]
ER  -