MK2 Inhibition Induces p53-Dependent Senescence in Glioblastoma Cells
Athena F Phoa, Ariadna Recasens, Fadi MS Gurgis, Tara A Betts, Sharleen V Menezes, Diep Chau, Kristiina Nordfors, Joonas Haapasalo, Hannu Haapasalo, Terrance G Johns, Brett W Stringer, Bryan W Day, Michael E Buckland, Najoua Lalaoui, Lenka Munoz
Cancers | MDPI | Published : 2020
MAPK-activated protein kinase 2 (MK2) has diverse roles in cancer. In response to chemotherapy, MK2 inhibition is synthetically lethal to p53-deficiency. While TP53 deletion is rare in glioblastomas, these tumors often carry TP53 mutations. Here, we show that MK2 inhibition strongly attenuated glioblastoma cell proliferation through p53wt stabilization and senescence. The senescence-inducing efficacy of MK2 inhibition was particularly strong when cells were co-treated with the standard-of-care temozolomide. However, MK2 inhibition also increased the stability of p53 mutants and enhanced the proliferation of p53-mutant stem cells. These observations reveal that in response to DNA damaging che..View full abstract
Awarded by National Health & Medical Research Council of Australia
Awarded by Cancer Australia
Awarded by Victorian Cancer Agency Mid-Career Fellowship
This research was funded by the National Health & Medical Research Council of Australia, grant number APP1163484. LM has been funded by the Cancer Institute NSW, AFP is supported by The University of Sydney RTP scholarship, NL is supported by Project grant #1145588 from the Cancer Australia and Cure Cancer Australia Foundation and the Victorian Cancer Agency Mid-Career Fellowship #17030.