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.