SSR2はGPX4と相互作用して鉄死を阻害することにより、ソラフェニブ耐性を促進する

Zebing Song¹, Mengdan Zhou¹, Xiaodong Song¹

¹Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Guangzhou Medical University. Guangzhou 510000, P.R. China.

Current molecular medicine

|January 22, 2026

要旨

Aim & Objectives:

Sorafenib is a first-line drug for hepatocellular carcinoma (HCC). Understanding the regulatory mechanisms of sorafenib resistance is critical to inhibit sorafenib resistance and develop novel therapeutic strategies. Here, we aimed to study the role of SSR2 (signal sequence receptor subunit 2) in sorafenib resistance of HCC.

Methods:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and cell viability assay were used to determine the role of SSR2 in sorafenib resistance of HCC. Co-immunoprecipitation (CoIP) was used to determine the interacting protein of SSR2.

Results:

We found SSR2 was upregulated in sorafenib-resistant HCC tissues. In addition, in HCC patients, SSR2 was associated with both poor response to sorafenib and poor clinical outcomes. Functional assay showed that SSR2 promoted sorafenib resistance in HCC cells. Mechanistically, SSR2 suppressed ferroptosis. Further analysis showed that SSR2 interacted with ferroptosis master regulator glutathione peroxidase 4 (GPX4) and increased the catalytic activity of GPX4, leading to inhibition of ferroptosis. Induction of ferroptosis could reverse the promotion effect of SSR2 overexpression on sorafenib resistance.

Discussion:

SRR2 plays a critical role in sorafenib resistance generation. However, the detailed mechanism of SRR2 increasing the catalytic activity of GPX4 will be further studied.

Conclusions:

In summary, we reveal that SSR2 enhances sorafenib resistance of HCC via interacting with GPX4 and inhibiting ferroptosis, providing a potential target for HCC treatment. The molecular mechanism of GPX4-SSR2 interaction in ferroptosis will be further studied.

キーワード:

GPX4 HCC治療 SSR2 鉄死肝細胞癌ソラフェニブ耐性

さらに関連する動画

11:56

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

Published on: October 25, 2013

14.7K

05:55

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System

Published on: December 21, 2019

7.2K

関連する概念動画

02:40

The Eukaryotic Promoter Region

18.7K

The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...

18.7K

02:40

The Eukaryotic Promoter Region

3.8K

00:46

Feedback Inhibition

56.9K

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!

56.9K

01:22

Resistivity

4.4K

When a voltage is applied to a conductor, an electrical field is generated, and charges in the conductor feel the force due to the electrical field. The current density that results depends on the electrical field and the properties of the material. In some materials, including metals at a given temperature, the current density is approximately proportional to the electrical field. In these cases, the current density can be modeled as:

4.4K

01:19

Resistance

5.7K

When a current moves through any conductor, the conductor causes some level of difficulty for the current to flow. The measure of that difficulty is known as the resistance of the material and is represented by R. Every material has its own resistance. In the case of conductors, heat is emitted whenever a current passes through them. Resistance depends on the resistivity of the material. Resistivity is a characteristic of the material used to fabricate electrical components, whereas the...

5.7K

01:30

Enzyme Inhibition

91.7K

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.

91.7K