Inhibition of WIP1 phosphatase sensitizes breast cancer cells to genotoxic stress and to MDM2 antagonist nutlin-3

• Published in: Oncotarget Vol. 7; no. 12; pp. 14458 - 14475
• Main Authors: Pechackova, Sona, Burdova, Kamila, Benada, Jan, Kleiblova, Petra, Jenikova, Gabriela, Macurek, Libor
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 22.03.2016
• Subjects: Aminopyridines - pharmacology; Apoptosis - drug effects; Breast Neoplasms - drug therapy; Breast Neoplasms - enzymology; Breast Neoplasms - pathology; Cell Cycle - drug effects; Cell Proliferation - drug effects; Dipeptides - pharmacology; DNA Damage - drug effects; Drug Resistance, Neoplasm; Female; Humans; Imidazoles - pharmacology; Piperazines - pharmacology; Protein Phosphatase 2C - antagonists & inhibitors; Protein Phosphatase 2C - genetics; Protein Phosphatase 2C - metabolism; Proto-Oncogene Proteins c-mdm2 - antagonists & inhibitors; Proto-Oncogene Proteins c-mdm2 - genetics; Proto-Oncogene Proteins c-mdm2 - metabolism; Research Paper; Tumor Cells, Cultured; Tumor Suppressor Protein p53 - metabolism; checkpoint; breast cancer; nutlin-3; WIP1 inhibitor; p53

PP2C family serine/threonine phosphatase WIP1 acts as a negative regulator of the tumor suppressor p53 and is implicated in silencing of cellular responses to genotoxic stress. Chromosomal locus 17q23 carrying the PPM1D (coding for WIP1) is commonly amplified in breast carcinomas and WIP1 was propos...