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CK2 blockade causes MPNST cell apoptosis and promotes degradation of β-catenin

Jed J Kendall1, Katherine E Chaney1, Ami V Patel1

  • 1Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital, Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA.

Oncotarget
|July 25, 2016
PubMed

Insights

CK2 inhibition shows promise for treating malignant peripheral nerve sheath tumors (MPNSTs). Targeting CK2 with CX-4945 reduced MPNST cell viability and slowed tumor growth in preclinical models.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas.
  • MPNSTs are a significant cause of mortality in Neurofibromatosis type 1 (NF1) patients.
  • Current therapeutic options for MPNSTs are limited, with surgical resection being the only curative approach.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting the CK2 enzyme in MPNSTs.
  • To determine if CK2 inhibition can impact the activated β-catenin signaling pathway crucial for MPNST survival.

Main Methods:

  • Assessed CK2α expression in MPNSTs.
  • Utilized the CK2 inhibitor CX-4945 (Silmitasertib) and CK2α-targeting shRNA to evaluate effects on MPNST cell viability.
  • Examined the impact on key signaling pathways, including β-catenin and TCF8.
  • Evaluated the efficacy of CX-4945 in vivo models.

Main Results:

  • CK2α was found to be over-expressed in MPNSTs.
  • Both CX-4945 and CK2α shRNA significantly reduced MPNST cell viability.
  • Inhibition of CK2 led to the destabilization of β-catenin and TCF8 signaling.
  • In vivo administration of CX-4945 demonstrated slowed tumor growth and extended survival.

Conclusions:

  • CK2 inhibition represents a promising therapeutic strategy for MPNSTs by targeting the β-catenin pathway.
  • Further research into combinatorial therapies may be necessary to achieve maximal efficacy against MPNSTs.
Keywords:
CK2G2 arrestMPNSTNF1β-catenin

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