Related Experiment Video

Updated: Jan 23, 2026

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
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Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

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SSR2 Promotes Sorafenib Resistance Via Interacting with GPX4 to Inhibit Ferroptosis

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
PubMed
Abstract

Insights

Signal sequence receptor subunit 2 (SSR2) promotes sorafenib resistance in hepatocellular carcinoma (HCC) by inhibiting ferroptosis. Targeting SSR2 may offer a new therapeutic strategy for HCC patients resistant to sorafenib.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Sorafenib is a key first-line treatment for hepatocellular carcinoma (HCC).
  • Understanding mechanisms of sorafenib resistance is crucial for improving HCC treatment outcomes.
  • Signal sequence receptor subunit 2 (SSR2) has emerged as a potential factor in cancer progression.

Purpose of the Study:

  • To investigate the role of SSR2 in sorafenib resistance in HCC.
  • To elucidate the molecular mechanisms underlying SSR2-mediated sorafenib resistance.

Main Methods:

  • Cell viability assays (MTT, colony formation) to assess SSR2's impact on sorafenib resistance.
  • Co-immunoprecipitation (CoIP) to identify SSR2 interacting proteins.
  • Functional assays to explore SSR2's effect on ferroptosis and its interaction with GPX4.

Main Results:

  • SSR2 was found to be upregulated in sorafenib-resistant HCC tissues and associated with poor clinical outcomes.
  • SSR2 overexpression promoted sorafenib resistance in HCC cells by suppressing ferroptosis.
  • SSR2 was shown to interact with glutathione peroxidase 4 (GPX4), enhancing its activity and inhibiting ferroptosis.

Conclusions:

  • SSR2 plays a significant role in the development of sorafenib resistance in HCC.
  • Targeting the SSR2-GPX4 interaction and its effect on ferroptosis presents a potential therapeutic strategy for overcoming sorafenib resistance in HCC.
Keywords:
GPX4HCC therapy.SSR2ferroptosishepatocellular carcinomasorafenib resistance

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