Emergence of protein kinase CK2 as a key target in cancer therapy.
Protein kinase CK2, a protein serine/threonine kinase, plays a global role in activities related to cell growth, cell death, and cell survival. CK2 has a large number of potential substrates localized in diverse locations in the cell including, for example, NF-kappaB as an important downstream target of the kinase. In addition to its involvement in cell growth and proliferation it is also a potent suppressor of apoptosis, raising its key importance in cancer cell phenotype. CK2 interacts with diverse pathways which illustrates the breadth of its impact on the cellular machinery of both cell growth and cell death giving it the status of a "master regulator" in the cell. With respect to cancer, CK2 has been found to be dysregulated in all cancers examined demonstrating increased protein expression levels and nuclear localization in cancer cells compared with their normal counterparts. We originally proposed CK2 as a potentially important target for cancer therapy. Given the ubiquitous and essential for cell survival nature of the kinase, an important consideration would be to target it specifically in cancer cells while sparing normal cells. Towards that end, our design of a tenascin based sub-50 nm (i.e., less than 50 nm size) nanocapsule in which an anti-CK2 therapeutic agent can be packaged is highly promising because this formulation can specifically deliver the cargo intracellularly to the cancer cells in vivo. Thus, appropriate strategies to target CK2 especially by molecular approaches may lead to a highly feasible and effective approach to eradication of a given cancer.
Trembley
Janeen H
JH
Cellular and Molecular Biochemistry Research Laboratory, Research Service, Minneapolis V.A. Medical Center, and Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55417, USA.
Chen
Zhong
Z
Unger
Gretchen
G
Slaton
Joel
J
Kren
Betsy T
BT
Van Waes
Carter
C
Ahmed
Khalil
K
D000818:Animals; D017209:Apoptosis; D047390:Casein Kinase II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D015398:Signal Transduction
D016328:NF-kappa B; D047390:Casein Kinase II