TY - JOUR
T1 - Transgenerational cell fate profiling
T2 - A method for the graphical presentation of complex cell cycle alterations
AU - Jemaà, Mohamed
AU - Galluzzi, Lorenzo
AU - Kepp, Oliver
AU - Castedo, Maria
AU - Rello-Varona, Santiago
AU - Vitale, Ilio
AU - Kroemer, Guido
N1 - Funding Information:
L.G. is funded by the LabEx ImmunoOncology. G.K. is supported by the Ligue Nationale contre le Cancer (Equipe labeli-sée), Agence Nationale pour la Recherche (ANR), European Commission (Active p53, Artforce, ChemoRes, ApopTrain), Fondation pour la Recherche Médicale (FRM), Institut National du Cancer (INCa), Cancéropôle Ile-de-France, AXA Research Fund and the Labex Immuno-Oncology.
PY - 2013/1/1
Y1 - 2013/1/1
N2 - The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized "transgenerational cell fate profiling." We speculate that this representation constitutes a valid alternative to classical "single-cell fate" and "genealogical" profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations.
AB - The illicit generation of tetraploid cells constitutes a prominent driver of oncogenesis, as it often precedes the development of aneuploidy and genomic instability. In addition, tetraploid (pre-)malignant cells display an elevated resistance against radio- and chemotherapy. Here, we report a strategy to preferentially kill tetraploid tumor cells based on the broad-spectrum kinase inhibitor SP600125. Live videomicroscopy revealed that SP600125 affects the execution of mitosis, impedes proper cell division and/or activates apoptosis in near-to-tetraploid, though less so in parental, cancer cells. We propose a novel graphical model to quantify the differential response of diploid and tetraploid cells to mitotic perturbators, including SP600125, which we baptized "transgenerational cell fate profiling." We speculate that this representation constitutes a valid alternative to classical "single-cell fate" and "genealogical" profiling and, hence, may facilitate the analysis of cell fate within a heterogeneous population as well as the visual examination of cell cycle alterations.
KW - Cell death
KW - Cytokinesis failure
KW - Microtubules
KW - Mitotic catastrophe
KW - Polyploidy
KW - Time-lapse microscopy
UR - http://www.scopus.com/inward/record.url?scp=84872339475&partnerID=8YFLogxK
U2 - 10.4161/cc.23046
DO - 10.4161/cc.23046
M3 - Article
AN - SCOPUS:84872339475
SN - 1538-4101
VL - 12
SP - 183
EP - 190
JO - Cell Cycle
JF - Cell Cycle
IS - 1
ER -