Abstract
PARP6 inhibition as a strategy to exploit centrosome clustering in cancer cells?
Highlights
Centrosomes function as the main microtubuleorganizing centers (MTOCs) and play an essential role during cellular mitosis
We recently reported the involvement of monoADP-ribosyltransferase PARP6 in maintaining centrosome integrity during mitosis by demonstrating that pharmacological inhibition of PARP6 induced multipolar spindle formation and elicited therapeutic effects in breast cancer [5]
Previous siRNA screens implicated PARP activity in centrosome clustering and bipolar spindle formation as a specific mitotic susceptibility in cancer cells [7]. We leveraged this knowledge and conducted parallel biochemical screens against multiple PARP enzymes together with cell-based phenotypic profiling in cancer cells to find that only PARP6 inhibition could drive multipolar spindle formation, with a strong correlation (R2 = 0.76) observed between PARP6 enzymatic inhibition and multipolar spindle induction potency
Summary
Centrosomes function as the main microtubuleorganizing centers (MTOCs) and play an essential role during cellular mitosis. We recently reported the involvement of monoADP-ribosyltransferase PARP6 in maintaining centrosome integrity during mitosis by demonstrating that pharmacological inhibition of PARP6 induced multipolar spindle formation and elicited therapeutic effects in breast cancer [5]. Previous siRNA screens implicated PARP activity in centrosome clustering and bipolar spindle formation as a specific mitotic susceptibility in cancer cells [7].
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