The effect of HMGB1 and RAGE on the clinicopathological and prognostic features of prostate cancer

Dao-Jun Lv

doi:10.20517/jtgg.2021.34

Abstract

As a DNA-binding protein, high mobility group box 1 (HMGB1) has been shown be involved in various biological activities, including transcription regulation, DNA repair, genomic stability, and extracellular signaling. Accumulating evidence indicates that HMGB1 has an important role in biological processes in cancer. Moreover, HMGB1 has been shown to have intracellular and extracellular roles, activating key cancerogenic signaling pathways. The main signal pathway is activated via the interaction of HMGB1 with its receptor, receptor for advanced glycation end-products (RAGE). In addition, overexpression of HMGB1/RAGE occurs in certain types of primary tumors and has been linked to increased metastasis and poorer prognosis. In our previous research, we demonstrated that co-expression of HMGB1 and RAGE is associated with cancer progression and poor patient outcome in prostate cancer (PCa). Together with the recent published evidence, we describe and speculate on the character of the HMGB1/RAGE axis in PCa progression and elaborate on future prospects for the application of potential strategies to target HMGB1 in PCa therapy.

Highlights

Prostate cancer (PCa) is one of the most frequent human malignancies and is the second leading cause of death by cancer in the western male population[1]
Studies from others and our group indicate that high mobility group box 1 (HMGB1) may play a crucial role in PCa progression
The interaction of HMGB1 with receptor for advanced glycation end-products (RAGE) indicates a central role of HMGB1 in PCa progression

Summary

Introduction

Prostate cancer (PCa) is one of the most frequent human malignancies and is the second leading cause of death by cancer in the western male population[1]. Extracellular HMGB1/RAGE interactions facilitate tumor proliferation via activation of p44/p42, p38, and SAPK/JNK MAPKs[17]. Recent publications show that targeting RAGE reduced the level of PSA, the downstream target gene of androgen receptor (AR)[29], indicating that RAGE may play a pivotal role in the regulation of AR in PCa cells.

Results

Conclusion