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Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach
11:11

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

Addiction to protein kinase CK2: a common denominator of diverse cancer cells?

Maria Ruzzene1, Lorenzo A Pinna

  • 1Department of Biological Chemistry and CNR Institute of Neurosciences, University of Padova, and Venetian Institute of Molecular Medicine (VIMM), Padova, Italy.

Biochimica Et Biophysica Acta
|August 12, 2009
PubMed

Insights

Casein kinase 2 (CK2) is constitutively active and elevated in many tumors, driving cancer by promoting survival and drug resistance. Cancer cells rely on high CK2 levels, making it a potential multi-purpose cancer treatment target.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Most oncogenic kinases are activated by genetic mutations, but Casein Kinase 2 (CK2) is constitutively active and lacks gain-of-function mutants.
  • CK2 is abnormally elevated in various tumors and acts as a cancer driver by promoting a pro-neoplastic cellular environment.

Purpose of the Study:

  • To investigate the role of CK2 in cancer development and its potential as a therapeutic target.
  • To explore the concept of "non oncogene addiction" in relation to CK2's role in cancer cell maintenance.

Main Methods:

  • Analysis of CK2's known functions in cancer, including anti-apoptotic and pro-survival roles, multi-drug resistance (MDR) enhancement, protection of the "onco-kinome", and promotion of neo-angiogenesis.
  • Review of studies demonstrating cancer cell dependence on high CK2 levels through the use of CK2 inhibitors and gene silencing.
  • Examination of cancer cells with genetic alterations in other oncokinases that are insensitive to specific CK2 inhibitors.

Main Results:

  • CK2 promotes cancer by enhancing cell survival, mediating multi-drug resistance, supporting the "onco-kinome", and promoting neo-angiogenesis.
  • Diverse cancer cells, including those with alterations in kinases like Abl and Alk, show reliance on high CK2 levels for survival.
  • Cancer cells exhibit "non oncogene addiction", depending on elevated CK2 levels for signaling network maintenance.

Conclusions:

  • CK2's constitutive activity and pro-cancer functions position it as a significant factor in neoplasia.
  • Cancer cells' dependence on elevated CK2 levels suggests a "non oncogene addiction" mechanism.
  • CK2 represents a promising "multi-purpose" therapeutic target for various tumor types.

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