Insights into the post-translational modification and its emerging role in shaping the tumor microenvironment

Abstract

More and more in-depth studies have revealed that the occurrence and development of tumors depend on gene mutation and tumor heterogeneity. The most important manifestation of tumor heterogeneity is the dynamic change of tumor microenvironment (TME) heterogeneity. This depends not only on the tumor cells themselves in the microenvironment where the infiltrating immune cells and matrix together forming an antitumor and/or pro-tumor network. TME has resulted in novel therapeutic interventions as a place beyond tumor beds. The malignant cancer cells, tumor infiltrate immune cells, angiogenic vascular cells, lymphatic endothelial cells, cancer-associated fibroblastic cells, and the released factors including intracellular metabolites, hormonal signals and inflammatory mediators all contribute actively to cancer progression. Protein post-translational modification (PTM) is often regarded as a degradative mechanism in protein destruction or turnover to maintain physiological homeostasis. Advances in quantitative transcriptomics, proteomics, and nuclease-based gene editing are now paving the global ways for exploring PTMs. In this review, we focus on recent developments in the PTM area and speculate on their importance as a critical functional readout for the regulation of TME. A wealth of information has been emerging to prove useful in the search for conventional therapies and the development of global therapeutic strategies.

Proteomic Profiling and Biomarker Discovery in Colorectal Liver Metastases

“…Enzymes and proteins involved in acetylation, typically on lysine residues, regulate many cellular physiological processes but are deregulated in cancer [ 98 ]. These alterations may have functional implications in cancer biology, such as metabolic reprogramming and adaptation to the tumour microenvironment [ 99 , 100 ]. Global-scale profiling of differentially expressed lysine-acetylated proteins in matched primary CRC and CRLM was first reported by Shen et al This study characterised the acetylome paired primary CRC and CRLM samples ( n = 3) using tandem mass tag protein labelling, high-affinity enrichment of acetylated peptides and LC-MS/MS analysis.…”

Exosome-Derived Non-Coding RNAs in the Tumor Microenvironment of Colorectal Cancer: Possible Functions, Mechanisms and Clinical Applications

“…TME is an important factor leading to the heterogeneity and targeted therapy of CRC ( 6 , 20 ). The composition of TME is influenced by both tumor features and patient state, which impacts disease progression, responsiveness to cancer therapy, and survival prognosis ( 21 ).…”

“…Tumor heterogeneity causes differences between and within CRC, which also increases the difficulty in the treatment of CRC ( 4 , 5 ). TME contributes significantly to this heterogeneity because it is the site of tumor cell formation and growth ( 6 , 7 ). TME is an intricate system, composed of primary cancer cells, associated stromal and immune cells, which considerably affects the behavior of CRC cells at the primary tumor site as well as in metastatic lesions ( 8 ).…”

Necroptosis-Related LncRNAs Signature and Subtypes for Predicting Prognosis and Revealing the Immune Microenvironment in Breast Cancer

“…The dynamic change in tumor microenvironment (TME) heterogeneity is considered to be the most important aspect of tumor heterogeneity, which depends on the tumor cells themselves in the microenvironment where the infiltrating immune cells and matrix together form an antitumor and/or pro-tumor network ( 4 ). The TME, a complex ecosystem composed of stromal cells, cancer cells, fibroblasts, chemokines, and immune cells ( 5 ), serves as a site of tumor cell growth and metastasis for promoting tumor immune escape, tumor growth, and metastasis ( 6 – 8 ), further influencing prognosis and prediction of response to specific treatments ( 9 ).…”