Protein Kinase C in Cancer Signaling and Therapy (Current Cancer Research)

Protein kinase C (PKC), a family of serine-threonine kinases, rocketed to the forefront of the cancer research field in the early 1980’s with its identification as an effector of phorbol esters, natural products with tumor-promoting activity. Phorbol esters had long been of interest to the cancer research field due to early studies in the mouse skin carcinogenesis model, which showed that prolonged topical application of phorbol esters promoted the formation of skin tumors on mice previously treated with mutagenic agents. Research in the last years has established key roles for PKC isozymes in the control of cell proliferation, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. It is now well established that the expression of PKC isozymes is altered in various types of cancers. More importantly, small molecule inhibitors have been developed with significant anti-cancer activity. The relevance of PKC isozymes in cancer signaling is therefore remarkable. Protein Kinase C in Cancer Signaling and Therapy is composed of twenty-three chapters written by leading experts in the field. The book is divided into four sections: Regulation of PKC isozyme function: from genes to biochemistry, PKC isozymes in the control of cell function, PKC isozymes in cancer, and PKC isozymes as targets for cancer therapy. Each section of Protein Kinase C in Cancer Signaling and Therapy begins with an introduction by an established professional in the field of Protein kinase C, followed by chapters that elucidate the importance of PKC in current cancer research. Front Matter....Pages i-xiv Front Matter....Pages 1-1 Protein Kinase C in Cancer Signaling and Therapy: Introduction and Historical Perspective....Pages 3-8 Regulation of Conventional and Novel Protein Kinase C Isozymes by Phosphorylation and Lipids....Pages 9-23 Phorbol Esters and Diacylglycerol: The PKC Activators....Pages 25-53 Diacylglycerol Signaling: The C1 Domain, Generation of DAG, and Termination of Signals....Pages 55-78 Regulation of PKC by Protein–Protein Interactions in Cancer....Pages 79-103 Front Matter....Pages 106-106 Introduction: PKC Isozymes in the Control of Cell Function....Pages 107-115 Regulation and Function of Protein Kinase D Signaling....Pages 117-154 PKC and Control of the Cell Cycle....Pages 155-188 PKC and the Control of Apoptosis....Pages 189-222 Atypical PKCs, NF-κB, and Inflammation....Pages 223-244 Front Matter....Pages 246-246 Introduction: PKC and Cancer....Pages 247-251 Protein Kinase C, p53, and DNA Damage....Pages 253-265 PKCs as Mediators of the Hedgehog and Wnt Signaling Pathways....Pages 267-286 PKC–PKD Interplay in Cancer....Pages 287-303 Transgenic Mouse Models to Investigate Functional Specificity of Protein Kinase C Isoforms in the Development of Squamous Cell Carcinoma, a Nonmelanoma Human Skin Cancer....Pages 305-321 PKC Isozymes and Skin Cancer....Pages 323-345 PKC and Breast Cancer....Pages 347-360 PKC and Prostate Cancer....Pages 361-378 Protein Kinase C and Lung Cancer....Pages 379-399 Front Matter....Pages 402-402 Introduction....Pages 403-407 Front Matter....Pages 402-402 PKC and Resistance to Chemotherapeutic Agents....Pages 409-429 PKCδ as a Target for Chemotherapeutic Drugs....Pages 431-453 Atypical PKCs as Targets for Cancer Therapy....Pages 455-484 Back Matter....Pages 485-494 Annotation Protein kinase C (PKC), a family of serine-threonine kinases, rocketed to the forefront of the cancer research field in the early 1980€™s with its identification as an effector of phorbol esters, natural products with tumor promoting activity. Phorbol esters had long been of interest to the cancer research field due to early studies in the mouse skin carcinogenesis model, which showed that prolonged topical application of phorbol esters promoted the formation of skin tumors on mice previously treated with mutagenic agents. Research in the last years has established key roles for PKC isozymes in the control of cell proliferation, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. Moreover, it is now well established that the expression of PKC isozymes is altered in various types of cancers. More importantly, small molecule inhibitors have been developed with significant anti-cancer activity. The relevance of PKC isozymes in cancer signaling is therefore remarkable.This book will have 4 sections. There will be 23 chapters. Each section will have a brief introduction by an expert in the field (~ 1-2 pages) Protein kinase C (PKC), a family of serine-threonine kinases, rocketed to the forefront of the cancer research field in the early 1980's with its identification as an effector of phorbol esters, natural products with tumor promoting activity. Phorbol esters had long been of interest to the cancer research field due to early studies in the mouse skin carcinogenesis model, which showed that prolonged topical application of phorbol esters promoted the formation of skin tumors on mice previously treated with mutagenic agents. Research in the last years has established key roles for PKC isozymes in the control of cell proliferation, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. Moreover, it is now well established that the expression of PKC isozymes is altered in various types of cancers. More importantly, small molecule inhibitors have been developed with significant anti-cancer activity. The relevance of PKC isozymes in cancer signaling is therefore remarkable. This book will have 4 sections. There will be 23 chapters. Each section will have a brief introduction by an expert in the field (~ 1-2 pages). The Protein Kinase C (PKC) serine-threonine kinases represent one & tile first families of signaling molecules implicated in carcinogenesis. Originally identified as the intracellular targets for the phorbol esters, natural products with tumor promoting activity, PKC isozymes rare known to mediate the actions of growth factors and hormones, and have been widely implicated in the control of cell proliferation, survival, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. Moreover, expression of PKC isozymes is altered in various types of cancers and correlates in many cases with the progression of the disease. Over-expression off KC isozymes in mouse models can lead to the development of cancer. PKCs also mediate the action of chemotherapeutic drugs or in some cases they are involved in the resistance to chemotherapeutic agents. More importantly, small molecule PKC inhibitors have been developed with significant anti-cancer activity. The relevance of fitC isozymes in cancer signaling is therefore remarkable Protein Kinase C in Cancer Signaling and Therapy is composed of twenty-three chapters written by leading experts in the field. The book is divided into four sections: Regulation of PKC isozyme function: from genes to biochemistry, PKC isozymes in the control of cell function, PKC isozymes in cancer, and PKC isozymes as targets for cancer therapy. Each section of Protein Kinase C in Cancer Signaling and Therapy begins with an introduction by an established professional in the field of PKC, followed by chapters that elucidate the importance of PKC in current cancer research. --Book Jacket