Abstract

PKC isozymes are involved in the modulation of cellular pathways related with tumor progression, acting as a suppressor or promoter. In cancer cells, PKCs are mutated, and most common type is loss of function. This paper focuses on the effect of PKCδ mutation in gastric cancer. LOF mutation occurs throughout catalytic and kinase domains of PKCδ, disrupting activation and function of kinase. In catalytic domain, there are various potential mutation targets, such as binding groove and zinc finger. Mutation residues detected in the kinase domain, such as DFG and APE motifs, can alter catalytic function, causing interruption of activation. Also, a critical region, called hinge region, modulates caspase-3 dependent cleavage, and such tyrosine mutation in this region reduces cleavage activity, inhibiting fully activation of kinase. Importantly, LOF mutation affects cellular activity of downstream protein, p53, through inhibiting transcription, localization, and phosphorylation. For instance, C1 domain mutant suppresses binding capacity with p53, reducing transcription of p53. Disruption of cellular component, tight junction, assembling related to PKC mutation. As identified, PKCδ correlates with ZO-1, and LOF mutation prevent translocation of ZO-1 to TJ area, leading to errors in TJ assembling, promoting tumor invasion.

Highlights

  • Protein Kinase C delta (PKCδ) is important in suppressing gastric cancer and a treatment target of several anti-cancer drugs

  • Within Tight junctions (TJs) proteins, PKCδ has been identified the role of regulation on ZO-1 [35], which are correlated with the progression with gastric cancer [36]

  • PKCδ is involved in several pathways related to proliferation or apoptosis, and the disruption of these regulations cause the progression of gastric cancer

Read more

Summary

Introduction

Protein Kinase C delta (PKCδ) is important in suppressing gastric cancer and a treatment target of several anti-cancer drugs. In gastric cancer cells, PKCδ is commonly loss of function (LOF) mutated [1]. This report will investigate potential mutation residues of PKCδ, and how LOF mutation affects pathways and association with other proteins related to gastric cancer. PKC family is involved in multiple mechanisms, including apoptosis, proliferation, and survival, importantly, affecting proteins associated with cancer progression and metastasis. Overall, considering the effect of PKCδ on proteins associated with cancer, δ isozyme is a tumor suppressor for gastric cancer. Various PKC isozymes has higher mutation rate in certain cancer types, such as PKCδ is commonly mutated in stomach cancer [1]. Newton revealed that most common mutation type for PKC in cancer cells was loss of function (LOF) [6]. Based on data from cBioPortal, all already documented mutations of PKCδ detected in stomach cancer may cause functionally lost in cancer cells [11]

Potential mutation sites of PKCδ in gastric caner
The effect of PKCδ LOF mutation on the p53
Disrruption of tight junction formation by PKCδ LOF mutation
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call