TY - JOUR
T1 - Atypical Protein Kinase Cι as a human oncogene and therapeutic target
AU - Parker, Peter J.
AU - Justilien, Verline
AU - Riou, Philippe
AU - Linch, Mark
AU - Fields, Alan P.
PY - 2014/3/1
Y1 - 2014/3/1
N2 - Protein kinase inhibitors represent a major class of targeted therapeutics that has made a positive impact on treatment of cancer and other disease indications. Among the promising kinase targets for further therapeutic development are members of the Protein Kinase C (PKC) family. The PKCs are central components of many signaling pathways that regulate diverse cellular functions including proliferation, cell cycle, differentiation, survival, cell migration, and polarity. Genetic manipulation of individual PKC isozymes has demonstrated that they often fulfill distinct, nonredundant cellular functions. Participation of PKC members in different intracellular signaling pathways reflects responses to varying extracellular stimuli, intracellular localization, tissue distribution, phosphorylation status, and intermolecular interactions. PKC activity, localization, phosphorylation, and/or expression are often altered in human tumors, and PKC isozymes have been implicated in various aspects of transformation, including uncontrolled proliferation, migration, invasion, metastasis, angiogenesis, and resistance to apoptosis. Despite the strong relationship between PKC isozymes and cancer, to date only atypical PKCiota has been shown to function as a bona fide oncogene, and as such is a particularly attractive therapeutic target for cancer treatment. In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer.
AB - Protein kinase inhibitors represent a major class of targeted therapeutics that has made a positive impact on treatment of cancer and other disease indications. Among the promising kinase targets for further therapeutic development are members of the Protein Kinase C (PKC) family. The PKCs are central components of many signaling pathways that regulate diverse cellular functions including proliferation, cell cycle, differentiation, survival, cell migration, and polarity. Genetic manipulation of individual PKC isozymes has demonstrated that they often fulfill distinct, nonredundant cellular functions. Participation of PKC members in different intracellular signaling pathways reflects responses to varying extracellular stimuli, intracellular localization, tissue distribution, phosphorylation status, and intermolecular interactions. PKC activity, localization, phosphorylation, and/or expression are often altered in human tumors, and PKC isozymes have been implicated in various aspects of transformation, including uncontrolled proliferation, migration, invasion, metastasis, angiogenesis, and resistance to apoptosis. Despite the strong relationship between PKC isozymes and cancer, to date only atypical PKCiota has been shown to function as a bona fide oncogene, and as such is a particularly attractive therapeutic target for cancer treatment. In this review, we discuss the role of PKCiota in transformation and describe mechanism-based approaches to therapeutically target oncogenic PKCiota signaling in cancer.
KW - Atypical Protein Kinase Cι
KW - Cellular transformation
KW - Mechanism-based therapeutics
KW - Oncogenic signaling
KW - Phox-Bem1 (PB1) domain
UR - http://www.scopus.com/inward/record.url?scp=84896733184&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84896733184&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2013.10.023
DO - 10.1016/j.bcp.2013.10.023
M3 - Comment/debate
C2 - 24231509
AN - SCOPUS:84896733184
SN - 0006-2952
VL - 88
SP - 1
EP - 11
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 1
ER -