@entity71665 -mediated checkpoint kinase control regulates proliferation and resistance to chemotherapy in XXXX .

@entity1 @entity15126 @entity981 @entity5 @entity23902 @entity876 @entity79 @entity421 @entity3 @entity71665 @entity9516
UNASSIGNED: Conventional high-grade @entity421 is the most common primary @entity79 , with relatively high incidence in young @entity1 . In this study we found that expression of @entity71665 correlates inversely with @entity3 -free survival in @entity421 @entity1 and is increased in @entity3 compared to primary @entity5 . @entity71665 is an adaptor protein that has been implicated in anti-apoptotic signalling and serves as an oncoprotein in @entity981 . In @entity421 cells, silencing @entity71665 triggered G2 cell-cycle arrest; @entity23902 protein levels were attenuated and @entity15126 - @entity23902 DNA damage response signalling in response to chemotherapy was abolished in @entity71665 -depleted @entity421 cells, while ATM, @entity9516 and @entity876 activation remained intact. @entity421 is notoriously difficult to treat with standard chemotherapy, and we examined whether pharmacological inhibition of the @entity71665 -controlled @entity15126 - @entity23902 response could sensitize @entity421 cells to genotoxic compounds. Indeed, pharmacological inhibitors targeting @entity23902 / @entity9516 or those selective for @entity23902 synergized with standard chemotherapy in 2D cultures. Likewise, in 3D extracellular matrix-embedded cultures, @entity23902 inhibition led to effective sensitization to chemotherapy. Together, these findings implicate @entity71665 in @entity15126 - @entity23902 signalling and point towards @entity23902 inhibition as a strategy to sensitize @entity1 @entity421 to chemotherapy. Copyright    2015 Pathological Society of Great Britain and Ireland. Published by John Wiley _ Sons, Ltd.
