The functions and regulatory pathways of S100A8/A9 and its receptors in cancers

Abstract

Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation. In the clinical setting, S100A8/A9 and its receptors can be used complementarily as efficient biomarkers for cancer diagnosis and treatment. This review comprehensively summarizes the biological functions of S100A8/A9 and its various receptors in tumor cells, in order to provide new insights and strategies targeting S100A8/A9 to promote novel diagnostic and therapeutic methods in cancers.

S100A8 is a prognostic signature and associated with immune response in diffuse large B-cell lymphoma

“…Essentially, the structures, localization, and TME of S100A8 are related to the complex capacity of various functions ( 14 , 16 – 18 ). In this study, S100A8 was enriched mainly in differential cell types, specifically macrophages, through scRNA-seq analysis using a public dataset, which contributed to the specific inflammatory milieu ( 19 ).…”

“…S100A8 (also called MRP-8 and Calgranulin A), which is a calcium-binding protein belonging to the S100 protein family with a low molecular weight (14)(15)(16), plays crucial roles in normal biological processes and pathological conditions (15,17). S100A8 that is located in the cytosol of resting phagocytes can be released by activated phagocytes and be followed by two independent translocation pathways (15,18). S100A8 could exhibit effects in inflammation, immune response, and cancer development, but its biological functions are complex.…”

Fecal calprotectin in pediatric gastrointestinal diseases: Pros and cons

“…Calprotectin inhibits many zinc-dependent enzymes, including matrix metalloprotease, inducing anti-proliferative & apoptosis effects in both normal and transformed cells[ 17 ]. Additionally, calprotectin modulates inflammatory responses by interacting with receptors like TLR4 and RAGE, influencing cytokine production and immune cell recruitment[ 18 ]. Moreover, it contributes to tissue homeostasis and repair by regulating cell differentiation and proliferation processes, thereby promoting wound healing[ 14 ].…”

A Spatial Transcriptomics Browser for Discovering Gene Expression Landscapes across Microscopic Tissue Sections

“…The mapping of the single gene(s) into the SOM gene map, on the other hand, reveals their location in or near modules D and C, respectively, which explains their similar ST patterns. Another group of genes and gene sets (e.g., AXL, HM angiogenesis, and HM inflammatory response) refers to the ST pattern associating with modules G and F. The gene S100A8 is reported to act as an early marker of melanoma development [59]. It upregulates in and near the keratinocyte region of the ST image (c11 and c10).…”