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Updated: Sep 17, 2025

Author Spotlight: Unveiling Transmembrane Protein Family-Related Markers in Gastric Cancer and Implications for Targeted Therapies
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Tumor-expressing PD-L1 regulates NT5E expression through MAPK/ERK pathway in triple-negative breast cancer

Cheng Cheng1,2,3, Chao Shi1,2, Shang Wu1,2

  • 1Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, 050000, China.

Oncology Research
|July 4, 2025
PubMed
Abstract

Insights

Programmed cell death ligand 1 (PD-L1) expressed by breast cancer cells regulates Ecto-5'-nucleotidase (NT5E) via the MAPK/ERK pathway. Inhibiting PD-L1 or NT5E reduces cancer cell proliferation and metastasis, offering new immunotherapy targets.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Programmed cell death 1 (PD-1) inhibitors have advanced cancer therapy.
  • The precise role and mechanisms of programmed cell death ligand 1 (PD-L1) in cancer cells remain incompletely understood.
  • Identifying novel therapeutic targets for breast cancer immunotherapy is crucial.

Purpose of the Study:

  • To investigate the function of PD-L1 within breast cancer cells.
  • To identify key molecular targets regulated by PD-L1 for future immunotherapy strategies.
  • To elucidate the signaling pathway through which PD-L1 influences its targets.

Main Methods:

  • RNA sequencing (RNA-seq) on PD-L1-silenced breast cancer cells to identify differentially expressed genes.
  • Bioinformatics analysis and immunohistochemistry on clinical breast cancer specimens.
  • In vitro validation including gene silencing (siRNA), Western blotting, and proliferation/metastasis assays.

Main Results:

  • A significant positive correlation was observed between Ecto-5 '-nucleotidase (NT5E) and PD-L1 expression in breast cancer.
  • High NT5E expression correlated with lymph node metastasis and poor overall survival (OS).
  • PD-L1 silencing reduced NT5E expression via the MAPK/ERK pathway; down-regulating either PD-L1 or NT5E inhibited cancer cell proliferation and metastasis.

Conclusions:

  • Tumor-expressed PD-L1 regulates NT5E through the MAPK/ERK signaling pathway.
  • Down-regulation of PD-L1 or NT5E significantly inhibits breast cancer cell proliferation and metastasis.
  • PD-L1 and NT5E represent potential therapeutic targets and prognostic markers for combined PD-L1 immunotherapy in breast cancer.
Keywords:
Breast cancerERKEcto-5′-nucleotidase (NT5E)MetastasisProgrammed cell death ligand 1 (PD-L1)Proliferation

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