Decatenation checkpoint defective melanomas are dependent on PI3K for survival

Brooks, Kelly, Ranall, Max, Spoerri, Loredana, Stevenson, Alex, Gunasingh, Gency, Pavey, Sandra, Meunier, Fred, Gonda, Thomas J. and Gabrielli, Brian (2014) Decatenation checkpoint defective melanomas are dependent on PI3K for survival. Pigment Cell and Melanoma Research, 27 5: 813-821. doi:10.1111/pcmr.12268

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Author Brooks, Kelly
Ranall, Max
Spoerri, Loredana
Stevenson, Alex
Gunasingh, Gency
Pavey, Sandra
Meunier, Fred
Gonda, Thomas J.
Gabrielli, Brian
Title Decatenation checkpoint defective melanomas are dependent on PI3K for survival
Journal name Pigment Cell and Melanoma Research   Check publisher's open access policy
ISSN 1755-1471
Publication date 2014-09-01
Sub-type Article (original research)
DOI 10.1111/pcmr.12268
Volume 27
Issue 5
Start page 813
End page 821
Total pages 9
Place of publication Malden, MA, United States
Publisher Wiley-Blackwell Publishing
Language eng
Formatted abstract
Melanoma cell lines are commonly defective for the G2 phase cell cycle checkpoint that responds to incomplete catenation of the replicated chromosomes. Here we demonstrate that melanomas defective for this checkpoint response are less sensitive to genotoxic stress, suggesting that the defective cells lines compensated for the checkpoint loss by increasing their ability to cope with DNA damage. We performed an siRNA kinome screen to identify kinases responsible, and identified PI3K pathway components. Checkpoint defective cell lines were three fold more sensitive to small molecule inhibitors of PI3K. The PI3K inhibitor PF-05212384 promoted apoptosis in the checkpoint defective lines, and the increased sensitivity to PI3K inhibition correlated with increased levels of activated Akt. This work demonstrates that increased PI3K pathway activation is a necessary adaption for the continued viability of melanomas with a defective decatenation checkpoint.
Keyword Decatenation checkpoint
Synthetic lethality
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article first published online: 23 JUN 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
School of Pharmacy Publications
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 6 times in Thomson Reuters Web of Science Article | Citations
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Created: Tue, 10 Jun 2014, 20:44:02 EST by Dr Sandra Pavey on behalf of UQ Diamantina Institute