The Multifunctional Protein Kinase C-ε in Cancer Development and Progression

Abstract

The protein kinase C (PKC) family proteins are important signal transducers and have long been the focus of cancer research. PKCɛ, a member of this family, is overexpressed in most solid tumors and plays critical roles in different processes that lead to cancer development. Studies using cell lines and animal models demonstrated the transforming potential of PKCɛ. While earlier research established the survival functions of PKCɛ, recent studies revealed its role in cell migration, invasion and cancer metastasis. PKCɛ has also been implicated in epithelial to mesenchymal transition (EMT), which may be the underlying mechanism by which it contributes to cell motility. In addition, PKCɛ affects cell-extracellular matrix (ECM) interactions by direct regulation of the cytoskeletal elements. Recent studies have also linked PKCɛ signaling to cancer stem cell functioning. This review focuses on the role of PKCɛ in different processes that lead to cancer development and progression. We also discussed current literatures on the pursuit of PKCɛ as a target for cancer therapy.

PKCϵ Is an Essential Mediator of Prostate Cancer Bone Metastasis

“…Emerging data from several laboratories established essential roles for PKCε in the progression of cancer, including prostate cancer (2, 5, 6, 10, 17). PKCε has been implicated in cell invasiveness, yet it is not clear whether this kinase plays a role in metastasis to the bone, a main site of prostate cancer cell dissemination.…”

“…Numerous laboratories underscored important roles for PKCε in cell cycle progression and the control of cell survival mechanisms (2, 5, 6). For example, forced expression of PKCε in LNCaP prostate cancer cells accelerates proliferation due to constitutive activation of the Erk cascade and protects cells against apoptotic stimuli (21, 22).…”

“…Although PKCs have been widely implicated in tumor promotion, it is now recognized that individual isozymes have distinctive roles in the progression of cancer, both in positive and negative manners (2-4). Among the different members of the PKC family, numerous studies in the last years unambiguously established PKCε as an oncogenic kinase and tumor biomarker (5, 6). Notably, PKCε is markedly up-regulated in epithelial cancers, including prostate, lung, breast, and head and neck cancer (2, 7-12).…”

Protein Kinase C Epsilon Cooperates with PTEN Loss for Prostate Tumorigenesis through the CXCL13-CXCR5 Pathway

“…Growth promoting, survival and transforming roles for PKCε have been identified in numerous cellular models. Consistent with these effects, PKCε activates mitogenic and survival pathways, namely Ras/Erk, PI3K/Akt, NF-κB and Stat3 (Aziz et al, 2007; Benavides et al, 2011; Garg et al, 2014; Jain and Basu, 2014; McJilton et al, 2003; Meshki et al, 2010; Mischak et al, 1993). PKCε also emerged as a positive regulator of cancer cell motility, invasion, and epithelial-mesenchymal transition (EMT) (Caino et al, 2012b; Garg et al, 2014; Jain and Basu, 2014).…”

“…PKCε up-regulation has been reported in a number of cancer types, potentially reflecting its involvement in disease etiology and progression (Aziz et al, 2007; Griner and Kazanietz, 2007; Jain and Basu, 2014; Pan et al, 2005). Growth promoting, survival and transforming roles for PKCε have been identified in numerous cellular models.…”