HSP70-eIF4G Interaction Promotes Protein Synthesis and Cell Proliferation in Hepatocellular Carcinoma.

Meng Wang,Baifeng Qian,Katrin Hoffmann,Kai Wei,Markus W Büchler,Svenja Feiler,Anastasia Lemekhova

doi:10.3390/cancers12082262

Meng Wang, Baifeng Qian + Show 5 more

Open Access

https://doi.org/10.3390/cancers12082262

Copy DOI

Journal: Cancers	Publication Date: Aug 13, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Heidelberg University

Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide and features various tumor escape mechanisms from treatment-induced stress. HSP70 plays a critical role in cell protection under stress. eIF4G physiologically regulates the formation of the protein-ribosomal complex and maintains cellular protein synthesis. However, the precise cooperation of both in HCC remains poorly understood. In this study, we demonstrate that HSP70 expression is positively correlated with eIF4G in tumor specimens from 25 HCC patients, in contrast to the adjacent non-tumorous tissues, and that both influence the survival of HCC patients. Mechanistically, this study indicates that HSP70 and eIF4G interact with each other in vitro. We further show that the HSP70–eIF4G interaction contributes to promoting cellular protein synthesis, enhancing cell proliferation, and inhibiting cell apoptosis. Collectively, this study reveals the pivotal role of HSP70–eIF4G interaction as an escape mechanism in HCC. Therefore, modulation of the HSP70–eIF4G interaction might be a potential novel therapeutic target of HCC treatment.

Highlights

Hepatocellular carcinoma (HCC), represents about 90% of primary liver tumors [1] and is the fifth most common malignancy worldwide [2]
HSP70 and eIF4G Expression Are Significantly Higher in HCC Tumor Specimens
To determine whether HSP70 and eIF4G expression are related to the clinicopathological characteristics of HCC patients, we divided 25 patients into two groups based on the protein expression levels of HSP70 and eIF4G

Summary

Introduction

Hepatocellular carcinoma (HCC), represents about 90% of primary liver tumors [1] and is the fifth most common malignancy worldwide [2]. Surgical resection is an efficient therapy that prolongs patient survival, but the five-year recurrence rate is still relatively high, at 70% [3,4,5]. Palliative treatment of advanced liver cancer with the oral multikinase inhibitor sorafenib leads to an overall survival (OS) of approximately 10.7 months (95% CI, 9.4 to 13.3) [6]. Within the HSPs family, HSP70 is the easiest to induce and increases dramatically under stress [9,10]. HSP70 plays a critical role in many unique features of malignant tumors, including uncontrolled proliferation, malignant transformation, and metastasis [17,18,19,20].

Methods

Results

Conclusion