Clinical significance of atypical protein kinase C (PKCι and PKCζ) and its relationship with yes-associated protein in lung adenocarcinoma

Abstract

Background Protein kinase C iota (PKCι) and protein kinase C zeta (PKCζ) are two atypical protein kinase (aPKC) enzymes that contribute to cell proliferation and cancer development. The Hippo/YAP pathway is commonly disrupted and upregulated in cancers. Herein, the expression patterns and clinical relevance of PKCι and PKCζ are evaluated in relation to YAP, a downstream effector of Hippo, in lung adenocarcinoma (LAC). The protein and mRNA expression levels of PKCι, PKCζ, YAP, and their phosphorylated forms, namely p-PKCι, p-PKCζ and p-YAP, are evaluated in relation to clinicopathological factors, including patient survival. Methods A total of 200 primary LAC tissue samples were examined by immunohistochemistry for PKCι, p-PKCι, PKCζ, p-PKCζ, YAP, and p-YAP protein expression. Sixty pairs of LAC and non-neoplastic lung tissue samples were assessed for PRKCI, PRKCZ, and YAP mRNA levels. PKCι, p-PKCι, PKCζ, and p-PKCζ protein expression were evaluated by Western blot analysis in the PC9 and PC9/GR LAC cell lines with YAP modulation. Results LAC demonstrated cytoplasmic PKCι, p-PKCι, PKCζ, and p-PKCζ immunostaining patterns. Positive aPKC protein expressions were related with poor patient survival. Especially, increased p-PKCι protein expression was significantly correlated with higher pathological stage and shortened overall survival. YAP overexpression contributes phosphorylation of PKCι and PKCζ protein expression in the LAC cell line. Conclusions PKCι and PKCζ are related to YAP in LAC. PKCι and PKCζ play distinct roles in LAC; specifically, p-PKCι overexpression is suggested to underlie factors that indicate a poor prognosis. Electronic supplementary material The online version of this article (10.1186/s12885-019-5992-7) contains supplementary material, which is available to authorized users.

The Effect of Interleukin-4 and Dexamethasone on RNA-Seq-Based Transcriptomic Profiling of Human Podocytes: A Potential Role in Minimal Change Nephrotic Syndrome

“…Along with PARD3, the aPKC complex is an essential regulator of podocyte morphology [ 43 ]. Protein kinase C Iota (PRKCI), which encodes protein kinase C iota, is an aPKC enzyme that contributes to cell proliferation [ 44 ]. As mentioned, structural maintenance of the slit diaphragm seems to be tightly regulated by polarity signaling pathways, and aPKC is an essential regulator of podocyte morphology [ 45 ].…”

Targeting Rho GTPase Signaling Networks in Cancer

“…Overexpression of PKCι has been observed in several human cancers, including gastric (Hashimoto et al, 2019), pancreatic (Scotti et al, 2010), breast (Rosse et al, 2014), ovarian (Tsang et al, 2017), prostate (Apostolatos et al, 2018), and lung cancer (Kim et al, 2019) and has been shown to act as an oncogenic driver in numerous studies (reviewed in Parker et al, 2014). The role of PKCξ in cancer is less clear, with both increased and decreased expression reported in human tumors (Garg et al, 2014).…”

Protein Kinase C as a Therapeutic Target in Non-Small Cell Lung Cancer

“…PKCι is similarly overexpressed in NSCLC tissues compared to normal lung epithelium [ 56 , 57 , 58 , 59 , 60 ]. Western blot analysis of NSCLC cell lines A549, H520, H1299, H292, ChaGo, and Sk-Mes1 showed high PKCι protein levels [ 59 , 61 ].…”

“…More recently, PKCζ upregulation has also been observed in NSCLC. PKCι and PKCζ are both reported to be downstream effectors of YAP, which regulates the phosphorylation of both atypical PKCs, promoting lung adenocarcinoma tumorigenesis [ 60 ]. The specific inhibition of PKCζ was previously shown to regulate NSCLC chemotaxis [ 71 ].…”