Ubiquitination and SUMOylation in the chronic inflammatory tumor microenvironment

Abstract

Cells and soluble mediators of the innate and adaptive immune systems are fundamental components of the tumor microenvironment. Nuclear factors, e.g. transcription factors (TFs) and oncoproteins/cancer suppressors, play important roles in controlling cytokine functions leading to the development, maintenance and metastasis of cancers. Studies focusing on the regulators of the pro-tumorigenic microenvironment are particularly pertinent to early diagnosis and potential development of targeted cancer therapeutics. This review is motivated by new insights into the molecular dynamics of ubiquitination and SUMOylation, which post-translationally modify tumor suppressor TFs, leading to initiation and progression of various cancers like prostate, colorectal, liver and breast cancers. These modification pathways are differentially modulated under various stimuli or stresses in order to sustain the oncogenic potentials. We deliberate on the vicious cycle of infection and chronic inflammation-driven processes of ubiquitination and SUMOylation, resulting in the imbalance in cytokine profiles in the pro-tumorigenic microenvironment.

Keywords: Cytokine profile; Inflammation-associated cancer; Small ubiquitin-like modifier (SUMO); Transcription factors; Tumor microenvironment; Ubiquitin-proteasome system (UPS).