HMGB1: an overview of its versatile roles in the pathogenesis of colorectal cancer

Abstract

Background In recent years, the high mobility group box-1 (HMGB1) protein, a damage-associated molecular pattern (DAMP) molecule, has been found to play multifunctional roles in the pathogenesis of colorectal cancer. Although much attention has been given to the diagnostic and prognostic values of HMGB1 in colorectal cancer, the exact functional roles of the protein as well as the mechanistic pathways involved have remained poorly defined. This systematic review aims to discuss what is currently known about the roles of HMGB1 in colorectal cancer development, growth and progression, and to highlight critical areas for future investigations. To achieve this, the bibliographic databases Pubmed, Scopus, Web of Science and ScienceDirect were systematically screened for articles from inception till June 2018, which address associations of HMGB1 with colorectal cancer. Conclusions HMGB1 plays multiple roles in promoting the pathogenesis of colorectal cancer, despite a few contradicting studies. HMGB1 may differentially regulate disease-related processes, depending on the redox status of the protein in colorectal cancer. Binding of HMGB1 to various protein partners may alter the impact of HMGB1 on disease progression. As HMGB1 is heavily implicated in the pathogenesis of colorectal cancer, it is crucial to further improve our understanding of the functional roles of HMGB1 not only in colorectal cancer, but ultimately in all types of cancers.

Data Driven Mathematical Model of Colon Cancer Progression

“…IL-10 is produced by macrophages [57,58], dendritic cells [54,59] and T-reg cells [52,56,60,61]. CCL20 is produced by macrophages [62].…”

“…On the other hand, multiple factors induced by cancer cells may promote natural death of dendritic cells [75][76][77][78][79] (black arrow in Figure 1 from cancer cells to DCs). Additionally, there's evidence that HMGB1 can reduce the maturation rate of dendritic cells [61,79]. Introducing the independent production rate of naive dendritic cells A D N , we get the following system for dynamics of naive (D N ) and activated (D) dendritic cells:…”

Biological functions and theranostic potential of HMGB family members in human cancers

“…They are confirmed to take part in different diseases, including inflammatory conditions, 4,16 autoimmune disease, 17 and cancers. 18,20 The roles and mechanisms of HMGB family members in different localizations may be various. HMGB1 can play pivotal roles in the nucleus, in the cytoplasm, on the membrane, and outside the cells.…”

“…HMGB1, which is involved in various cascades, can also regulate metastasis. 18 Epithelial-mesenchymal transition (EMT) is a cellular process in which epithelial cells lose cell-cell contacts and apical-basal polarity and acquire the mesenchymal phenotype. These alterations result in reduced interactions among cells and increased invasive capacities.…”

High Mobility Group Box 1 in Human Cancer

“…Malignancies in which HMGB1 has been reported to play a prominent role in disease pathogenesis, albeit often involving variable mechanisms operating at different stages of tumorigenesis, include non-small cell lung cancer (NSCLC) [ 99 ], metastatic pancreatic ductal adenocarcinoma [ 100 , 101 ], metastatic breast cancer [ 21 , 102 ], epithelial ovarian cancer [ 103 ], hepatocellular carcinoma (HCC) [ 104 , 105 ], colorectal cancer [ 106 , 107 ], metastatic melanoma [ 108 ], esophageal squamous cell carcinoma [ 109 ], malignant mesothelioma [ 110 ] and glioblastoma [ 111 ].…”