Endoplasmic reticulum stress: Multiple regulatory roles in hepatocellular carcinoma

Abstract

Background: Endoplasmic reticulum (ER) stress is a basic cellular stress response that maintains cellular protein homeostasis under endogenous or exogenous stimuli, which depends on the stimulus, its intensity, and action time. The ER produces a corresponding cascade reaction for crosstalk of adaptive and/or pro-death regulation with other organelles. Hepatocellular carcinoma(HCC) is one of the most common malignant solid tumors with an extremely poor prognosis. Viral hepatitis infection, cirrhosis, and steatohepatitis are closely related to the occurrence and development of HCC, and ER stress has gradually been shown to be a major mechanism. Moreover, an increasing need for protein and lipid products and relative deficiencies of oxygen and nutrients for rapid proliferation and endoplasmic reticulum stress are undoubtedly involved. Therefore, to fully and comprehensively understand the regulatory role of endoplasmic reticulum stress in the occurrence and progression of HCC is of vital importance to explore its pathogenesis and develop novel anti-cancer strategies.

Methodology: We searched for relevant publications in the PubMed databases using the keywords "Endoplasmic reticulum stress", "hepatocellular carcinoma" in last five years,and present an overview of the current knowledge that links ER stress and HCC, which includes carcinogenesis, progression, and anti-cancer strategies, and propose directions of future research.

Result: ER stress were confirmed to be multiple regulators or effectors of cancer, which also be confirmed to drive tumorigenesis and progression of HCC. Targeting ER stress signaling pathway and related molecules could play a critical role for anti-HCC and has become a research hotspot for anti-cancer in recent years.

Conclusion: ER stress are critical for the processes of the tumorigenesis and progression of tumors. For HCC, ER stress was associated with tumorigenesis, development, metastasis, angiogenesis and drug resistance, targeting ER stress has emerged as a potential anti-tumor strategy.

Keywords: Endoplasmic reticulum stress; Hepatocellular carcinoma; UPR, Anti-cancer therapy.