Receptor for Advanced Glycation End Products Acts as a Fuel to Colorectal Cancer Development

Abstract

Receptor for advanced glycation end-products (RAGE) is a multiligand binding and single-pass transmembrane protein taken in diverse chronic inflammatory conditions. RAGE behaves as a pattern recognition receptor, which binds and is engaged in the cellular response to a variety of damage-associated molecular pattern molecules, as well as HMGB1, S100 proteins, and AGEs (advanced glycation end-products). The RAGE activation turns out to a formation of numerous intracellular signaling mechanisms, resulting in the progression and prolongation of colorectal carcinoma (CRC). The RAGE expression correlates well with the survival of colon cancer cells. RAGE is involved in the tumorigenesis, which increases and develops well in the stressed tumor microenvironment. In this review, we summarized downstream signaling cascade activated by the multiligand activation of RAGE, as well as RAGE ligands and their sources, clinical studies, and tumor markers related to RAGE particularly in the inflammatory tumor microenvironment in CRC. Furthermore, the role of RAGE signaling pathway in CRC patients with diabetic mellitus is investigated. RAGE has been reported to drive assorted signaling pathways, including activator protein 1, nuclear factor-κB, signal transducer and activator of transcription 3, SMAD family member 4 (Smad4), mitogen-activated protein kinases, mammalian target of rapamycin, phosphoinositide 3-kinases, reticular activating system, Wnt/β-catenin pathway, and Glycogen synthase kinase 3β, and even microRNAs.

Increase of α-dicarbonyls in liver and receptor for advanced glycation end products on immune cells are linked to nonalcoholic fatty liver disease and liver cancer

“…15 To date, there are already several literature overviews supporting a direct link between α-dC -AGE/AGE-proteins and the activation of RAGE 16,17 as well as a recent review on colorectal cancer describing the involvement of AGEs and their precursors (α-dC) and, especially, RAGE in cancer progression. 57 RAGE, a multiligand cell surface receptor, has been reported to correlate with the poor therapeutic outcomes and malignancy of HCC as comprehensively reviewed by Takino et al 58 Moreover, in the same study, the researchers underlined that interactions between toxic AGEs and RAGE-induced oxidative stress, which may in turn lead to adverse effects in tumor cells and HSC during liver disease progression. 58 In their study, Li and colleagues confirmed RAGE overexpression in HCC and its important role in cancerous disease progression, associated with proliferation and resistance to sorafenib.…”

“… 15 To date, there are already several literature overviews supporting a direct link between α-dC – AGE/AGE-proteins and the activation of RAGE 16 , 17 as well as a recent review on colorectal cancer describing the involvement of AGEs and their precursors (α-dC) and, especially, RAGE in cancer progression. 57 …”

Role of Glycated High Mobility Group Box-1 in Gastric Cancer

“…Both HMGB1 and AGE bind to RAGE [ 12 ]. We have previously reported the differences between HMGB1 and AGE as RAGE ligands [ 5 ].…”

“…It is a cell membrane receptor that has the ability to bind to multiple ligands, such as AGE, HMGB1, and S100B [ 11 ]. HMGB1 enhances oxidative stress by binding to RAGE via multiple pathways, such as mitogen-activated protein kinase, p21ras, nuclear factor (NF)-κB, AKT, phosphoinositide 3-kinase, and Wnt [ 12 ]. Importantly, RAGE also binds to AGE [ 13 , 14 ], which is generated at high levels in diabetes mellitus.…”

Toxicity of advanced glycation end products (Review)

“…RAGE expression is upregulated in a vast majority of cancers, but its expression is very low under physiological conditions. Specific examples of types of cancer in which RAGE expression is upregulated include colorectal cancer ( 32 ), pancreatic cancer ( 33 ), prostate cancer ( 34 ), lung cancer ( 35 ) and breast cancer, and in breast cancer, it has been reported that the RAGE rs1800624 polymorphism may increase the risk of breast cancer ( 36 ).…”