Protein Kinase C Signaling in Carcinogenesis

Abstract

Protein kinase C (PKC) is a family of serine-threonine kinases that plays an essential role in diverse physiological processes. As such, dysregulation of these kinases results in a number of pathological conditions including cancer. Functional studies have shed light on key PKC signaling pathways that contribute to maintaining survival, growth, and metastatic potential of cancer cells. Targeting specific PKC isoforms is effective at inhibiting cancer development and progression in animal models, providing proof of concept that the members of the PKC family are potentially promising therapeutic targets. Unfortunately, to date there is limited success in generating efficacious and safe PKC modulators mainly due to the high structural conservation among PKC members. An additional challenge is effectively targeting a single PKC isoform in the context of the complex interplay among the isoforms in specific tissues and cancer subtypes. Recent findings on isoform-specific binding partners provide us with an opportunity to control the activity of a single isoform without affecting others. Moving forward, there is potential to utilize specific PKC isoforms as prognostic and predictive biomarkers to guide therapeutic choice and predict response to treatment.