TY - JOUR
T1 - Nuclear localization of the caspase-3-cleaved form of p73 in anoikis
AU - Alsafadi, Samar
AU - Tourpin, Sophie
AU - Bessoltane, Nadia
AU - Salomé-Desnoulez, Sophie
AU - Vassal, Gilles
AU - André, Fabrice
AU - Ahomadegbe, Jean Charles
PY - 2016/3/15
Y1 - 2016/3/15
N2 - The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis caused by inadequate cell-matrix interactions. Breast cancer cell lines with different p53 status were treated with doxorubicin (DOX) or docetaxel (DOC) and cells detached from the extracellular matrix were analyzed. We demonstrate for the first time that DOX-induced cell detachment is associated with p73 cleavage and caspase activation, independently of the p53 status. However, we did not detect p73 cleavage or caspase activation in detached cells under DOC treatment. Overexpressing the apoptotic isoform of p73 led to cell detachment associated with p73 cleavage and caspase activation. Interestingly, p73 cleaved forms localize to the nucleus during the late phase of cell death indicating an increase in the transcriptional activity. Our study suggests that the cleavage of p73 on specific sites may release its pro-apoptotic function and contribute to cell death.
AB - The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis caused by inadequate cell-matrix interactions. Breast cancer cell lines with different p53 status were treated with doxorubicin (DOX) or docetaxel (DOC) and cells detached from the extracellular matrix were analyzed. We demonstrate for the first time that DOX-induced cell detachment is associated with p73 cleavage and caspase activation, independently of the p53 status. However, we did not detect p73 cleavage or caspase activation in detached cells under DOC treatment. Overexpressing the apoptotic isoform of p73 led to cell detachment associated with p73 cleavage and caspase activation. Interestingly, p73 cleaved forms localize to the nucleus during the late phase of cell death indicating an increase in the transcriptional activity. Our study suggests that the cleavage of p73 on specific sites may release its pro-apoptotic function and contribute to cell death.
KW - Anoikis
KW - Cleaved p73
KW - Nuclear localization
UR - http://www.scopus.com/inward/record.url?scp=84962850827&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.6329
DO - 10.18632/oncotarget.6329
M3 - Article
C2 - 26575022
AN - SCOPUS:84962850827
SN - 1949-2553
VL - 7
SP - 12331
EP - 12343
JO - Oncotarget
JF - Oncotarget
IS - 11
ER -