Abstract
Protein Kinase C theta (PKCθ) is a serine/threonine kinase that belongs to the novel PKC subfamily. In normal tissue, its expression is restricted to skeletal muscle cells, platelets and T lymphocytes in which PKCθ controls several essential cellular processes such as survival, proliferation and differentiation. Particularly, PKCθ has been extensively studied for its role in the immune system where its translocation to the immunological synapse plays a critical role in T cell activation. Beyond its physiological role in immune responses, increasing evidence implicates PKCθ in the pathology of various diseases, especially autoimmune disorders and cancers. In this review, we discuss the implication of PKCθ in various types of cancers and the PKCθ-mediated signaling events controlling cancer initiation and progression. In these types of cancers, the high PKCθ expression leads to aberrant cell proliferation, migration and invasion resulting in malignant phenotype. The recent development and application of PKCθ inhibitors in the context of autoimmune diseases could benefit the emergence of treatment for cancers in which PKCθ has been implicated.
Highlights
The Protein Kinase C (PKC) family is a family of serine/threonine kinases that are involved in various cellular processes for different cell types
The regulatory and tory and catalytic domains are separated by a hinge region, called the V3 motif, which is catalytic domains are separated by a hinge region, called the V3 motif, which is unique unique and highly specific to each PKC isoforms
We and other groups found that PKCθ was highly expressed in estrogen receptor negative (ER−) human breast tumors at transcript [47,48] and protein levels [49], whereas it was not expressed in normal breast epithelia and weakly expressed in ER+ breast tumors
Summary
The Protein Kinase C (PKC) family is a family of serine/threonine kinases that are involved in various cellular processes for different cell types. This classification is based on their structure and ability to respond to calcium and/or diacylglycerol (DAG) [1] Among this family, the novel PKCθ isoform is different from other PKC isoforms since its physiological expression is limited to a few types of cells, such as T cells, platelets and skeletal muscle cells. In the last decade, growing evidence implicated the PKCθ signaling in the biology of cancer where it controls cancer cell proliferation, migration and invasion at the cytoplasmic or nuclear levels We discuss this emerging function of PKCθ in cancer by analyzing its diverse modes of action and their consequence on critical biological processes involved in tumorigenesis and cancer progression
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