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SLC3A1 Mitigates Ferroptosis and Promotes Enzalutamide Resistance in Prostate Cancer

Peng Liu1, Haocheng Zhang1, Yuhang Qian1

  • 1Department of Urology, 411 Hospital of Shanghai University, Shanghai, China.

Journal of Biochemical and Molecular Toxicology
|August 17, 2026
PubMed

Insights

This study reveals solute carrier family 3 member 1 (SLC3A1) drives enzalutamide resistance in prostate cancer. Targeting SLC3A1 may overcome treatment challenges in advanced prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Prostate cancer (PCa) is a major cause of mortality in aging males.
  • Enzalutamide (Enza) resistance presents a significant therapeutic hurdle in PCa management.
  • Identifying novel targets is crucial for overcoming treatment resistance.

Purpose of the Study:

  • To identify key molecular drivers of enzalutamide resistance in prostate cancer.
  • To investigate the role of SLC3A1 in conferring resistance to enzalutamide.
  • To explore SLC3A1 as a potential therapeutic target for advanced PCa.

Main Methods:

  • Integrative bioinformatics analysis of Gene Expression Omnibus (GEO) datasets.
  • Weighted gene co-expression network analysis (WGCNA).
  • Single-cell RNA sequencing (scRNA-seq).
  • In vitro and in vivo functional experiments, including gene knockdown and overexpression.

Main Results:

  • SLC3A1 was significantly upregulated in enzalutamide-resistant PCa models.
  • SLC3A1 expression correlated with adverse prognosis and activation of survival pathways.
  • SLC3A1 knockdown inhibited proliferation and AKT phosphorylation in LNCaP cells.
  • SLC3A1 overexpression activated PI3K-AKT signaling, suppressed ferroptosis, and conferred enzalutamide resistance.

Conclusions:

  • SLC3A1 is a critical mediator of enzalutamide resistance in prostate cancer.
  • Targeting SLC3A1 presents a promising strategy to overcome therapeutic resistance in advanced PCa.
  • The PI3K-AKT pathway and ferroptosis regulation are implicated in SLC3A1-mediated resistance.
Keywords:
GEOSLC3A1WGCNAenzalutamideprostate cancer

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