Protein Kinase C (PKC) Isozymes and Cancer

Abstract

Protein kinase C (PKC) is a family of phospholipid-dependent serine/threonine kinases, which can be further classified into three PKC isozymes subfamilies: conventional or classic, novel or nonclassic, and atypical. PKC isozymes are known to be involved in cell proliferation, survival, invasion, migration, apoptosis, angiogenesis, and drug resistance. Because of their key roles in cell signaling, PKC isozymes also have the potential to be promising therapeutic targets for several diseases, such as cardiovascular diseases, immune and inflammatory diseases, neurological diseases, metabolic disorders, and multiple types of cancer. This review primarily focuses on the activation, mechanism, and function of PKC isozymes during cancer development and progression.

PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

“…Therefore, exploring the underlying mechanism of ROS generation would help in understanding hepatocellular carcinogenesis and providing new therapeutic targets. PKC was originally recognized as a major player in cellular signal transduction, and accumulating evidence have confirmed the involvement of PKC isozymes in mitogenesis, survival and malignant transformation through their increased or decreased participation in various cellular signaling pathways [23]. In this study, our data demonstrate that PKCa, but not PKCbI or PKCbII, promoted ROS production in HCC cells.…”

Tetraspanins Function as Regulators of Cellular Signaling

“…PKCs can phosphorylate several targets, including the myosin light chain II (Liu X. et al, 2013), PKD2 (Waldron et al, 2001; Navarro and Cantrell, 2014), Ras GEFs (Jun et al, 2013), and the β1 integrin tail (Stawowy et al, 2005), which collectively contribute to the regulation of cell proliferation, apoptosis, and adhesion amongst other cellular behaviors (Kang, 2014). The interaction between tetraspanins and PKC was originally demonstrated in K562 cells using an elaborate series of immunoprecipitation experiments (Zhang et al, 2001).…”

Cancer-Associated Protein Kinase C Mutations Reveal Kinase’s Role as Tumor Suppressor

“…PKC has proved an intractable target in cancer therapeutics (Kang, 2014). PKCι was proposed to be an oncogene in lung and ovarian cancers (Justilien et al, 2014; Regala et al, 2005; Zhang et al, 2006), and PKCε was categorized as an oncogene because of its ability to transform cells (Cacace et al, 1993).…”