Related Experiment Video

Updated: Apr 9, 2026

Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells
05:58

Site-Specific Lysine Lactylation via Genetic Code Expansion in E. coli and Mammalian Cells

Published on: February 24, 2026

248

Secretory autophagy mediates SLC16A3/MCT4-dependent lactate secretion to drive metastatic progression in

Shan-Ying Wu1,2, Hung-Ju Lin3,4, Kai-Ying Lan1,3

  • 1Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

Autophagy
|April 8, 2026
PubMed

Insights

Epidermal growth factor (EGF) signaling drives triple-negative breast cancer (TNBC) metastasis via secretory autophagy. This pathway enhances lactate transport, promoting tumor spread and poor survival, offering a novel therapeutic target.

Area of Science:

  • Oncology
  • Cell Biology
  • Metabolism

Background:

  • Triple-negative breast cancer (TNBC) is characterized by hyperactive epidermal growth factor (EGF) signaling, which promotes metabolic plasticity and metastasis.
  • Secretory autophagy is identified as a critical downstream mediator linking EGF signaling to metabolic reprogramming in TNBC.

Purpose of the Study:

  • To elucidate the role of secretory autophagy in mediating EGF-driven metabolic changes and metastasis in TNBC.
  • To investigate the molecular mechanisms by which EGF signaling activates secretory autophagy and influences lactate transport.

Main Methods:

  • Utilized TNBC cell lines and orthotopic mouse models.
  • Stimulated EGF signaling and analyzed autophagosome trafficking via SEC22B-dependent routes.
  • Performed proteomic profiling of purified autophagosomes.
  • Investigated the interaction between MAP1LC3/LC3 and SLC16A3/MCT4.
  • Blocked autophagy genetically or pharmacologically.
  • Assessed SLC16A3 surface localization, lactate efflux, and lung metastasis.
  • Conducted multiplex immunofluorescence on patient tumor samples.

Main Results:

  • EGF stimulation activated secretory autophagy, redirecting autophagosomes to the plasma membrane.
  • Autophagosomes were enriched with lactate transporter SLC16A3/MCT4 and its chaperone BSG/CD147.
  • EGF promoted LC3-SLC16A3 interaction, enhancing SLC16A3 plasma membrane trafficking and lactate efflux.
  • Autophagy blockade suppressed SLC16A3 surface localization, reduced lactate secretion, and inhibited lung metastasis.
  • Co-expression of EGFR, LC3, and SLC16A3 in patient tumors correlated with poor disease-free survival.

Conclusions:

  • A novel EGF-secretory autophagy axis regulates metabolic remodeling in TNBC, driving metastasis.
  • Targeting the secretory autophagy-SLC16A3-lactate pathway presents a promising therapeutic strategy for TNBC.
  • The findings highlight the clinical relevance of this pathway, with co-expression linked to adverse outcomes.
Keywords:
Lactate secretionSLC16A3/MCT4TNBCmetastasissecretory autophagytumor microenvironment

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