Contributing Role of High Mobility Group Box 1 Signaling in Oral Cancer Development and Therapy

Abstract

Oral squamous cell carcinoma (OSCC) is the most frequent type of oral cancer of multifactorial origin, characterized by histological and clinical manifestations. To date, there are no specific biomarkers or treatment modalities available to efficiently manage this neoplasia, demanding further research on the molecular background of OSCC pathology. Elucidation of signal transduction pathways and associated molecules with differential expression and function in OSCC are expected to enhance the future development of molecular targeted therapies. Among signaling proteins with a potential functional role in OSCC, the High Mobility Group Box 1 (HMGB1) protein has stimulated scientific interest due to frequent upregulation, and implication in the progression of many types of head and neck cancer types. HMGB1 is a nuclear nonhistone protein and an extracellularly secreted cytokine that can interact with several signaling molecules implicated in the pathogenic pathways of OSCC. Binding of HMGB1 to specific receptors on OSCC cells such as the receptor of AGE (RAGE) and the toll-like receptor (TLR) has been shown to initiate several intercellular signaling cascades that can promote OSCC growth, invasion, and metastasis, indicating a potential target for patient prognosis and therapeutic approaches. The purpose of this review is to explore the functional role and associated signaling of HMGB1 in OSCC in order to reveal potential therapeutic targeting options.

Ferroptosis and HMGB2 induced calreticulin translocation required for immunogenic cell death are controlled by the nuclear exporter XPO1

“…It has been reported that HMGB1 can be secreted into the circulation in numerous diseases including neurodegeneration 10 , Alzheimer disease 11 , lung disease 12 , and a wide range of cancers including gastric cancer 13 , colorectal cancer 13,14 , hepatocellular carcinoma 13 , pancreatic cancer 13,15 , nasopharyngeal carcinoma 13 , head and neck squamous-cell carcinoma 13,16 , esophageal cancer 13 , malignant pleural mesothelioma 13 , bladder cancer 13 , prostate cancer 13,17 , ovarian cancer 17 , lung cancer 18 , and cervical carcinoma 13 . Fewer studies have examined the secretion of HMGB2 19 , although it was recently discovered that nuclear HMGB2 makes an important contribution to the differentiation and survival of functional memory cells and stem-like progenitor exhausted T cells 20 .…”

Fabrication of a Three-Dimensional Spheroid Culture System for Oral Squamous Cell Carcinomas Using a Microfabricated Device

“…Squamous cell carcinoma is the most frequent histological type of oral cancer [8,9]. CSCs in head and neck squamous cell carcinoma possess enhanced invasive and metastatic potential and resistance to therapies, contributing to lethality [10].…”