bims-nocaut Biomed News
on Non-canonical autophagy
Issue of 2026–04–12
two papers selected by
Quentin Frenger, University of Strasbourg
  1. Autophagic extracellular vesicles: a distinct secretory route linking autophagy to extracellular communication.
  2. Secretory autophagy mediates SLC16A3/MCT4-dependent lactate secretion to drive metastatic progression in triple-negative breast cancer.
  1. Autophagy. 2026 Apr 09.
    Autophagic extracellular vesicles: a distinct secretory route linking autophagy to extracellular communication.
    Hongqi Wei, Yuxuan Fu.
      Macroautophagy/autophagy is classically defined as a degradative pathway that delivers cytoplasmic material to lysosomes. However, accumulating evidence indicates that autophagy can also support unconventional secretion. A recent study identifies a previously unrecognized subtype of small extracellular vesicles termed autophagic extracellular vesicles (AEVs). These vesicles originate from amphisomes formed by the fusion of autophagosomes with multivesicular bodies and are characterized by a size below 100 nm together with the presence of autophagic cargos, ESCRT-III components and RAB13. Importantly, biogenesis of AEVs is distinct from that of classical exosomes, which requires specific components of the ESCRT III complex and the GTPase RAB27A. The further finding that enterovirus can exploit AEVs to infect receptor-negative cells, thereby expanding viral tropism, suggests that secretory autophagy serves as a pivotal mechanism driving pathogen dissemination. This work provides the conceptual framework of extracellular vesicle heterogeneity and positions secretory autophagy as an important contributor to intercellular communication.
    Keywords:  Amphisomes; ESCRT-III; RAB13; autophagic extracellular vesicles (AEVs); enterovirus; secretory autophagy
    DOI:  https://doi.org/10.1080/15548627.2026.2658229
  2. Autophagy. 2026 Apr 08.
    Secretory autophagy mediates SLC16A3/MCT4-dependent lactate secretion to drive metastatic progression in triple-negative breast cancer.
    Shan-Ying Wu, Hung-Ju Lin, Kai-Ying Lan, Hong-Chen Chen, Chao-Hsiung Lin, Chih-Yi Hsu, Yi-Jang Lee, Yen-Yu Chou, Yeh-Shiu Chu, Wei-Chung Chiang, Hsiao-Sheng Liu, Yuan-Chieh Yeh, Sheng-Hui Lan.
      Triple-negative breast cancer (TNBC) exhibits hyperactive EGF (epidermal growth factor) signaling that drives metabolic plasticity and metastasis. Here, we identify secretory macroautophagy/autophagy as a key downstream effector linking EGF signaling to metabolic reprogramming that fuels TNBC metastatic progression. In TNBC cells, EGF stimulation redirected autophagosomes toward the plasma membrane through a SEC22B-dependent route, signifying activation of secretory autophagy. Proteomic profiling of purified autophagosomes revealed enrichment of the lactate transporter SLC16A3/MCT4 and its chaperone BSG/CD147 on autophagosomal membranes. Mechanistically, EGF promoted MAP1LC3/LC3-SLC16A3 interaction, facilitating SLC16A3 trafficking to the plasma membrane and enhancing lactate efflux. Genetic or pharmacological blockade of autophagy abrogated SLC16A3 surface localization, reduced extracellular lactate accumulation, and markedly suppressed lung metastasis originating from orthotopic TNBC tumors in mice. Although pharmacological inhibition of SLC16A3 effectively blocks its transporter activity and reduces lactate secretion, targeting autophagy provides a more precise approach to suppress EGF-driven SLC16A3 expression and the consequent rise in lactate secretion. Clinically, multiplex immunofluorescence of patient tumors demonstrated strong co-expression of EGFR, LC3, and SLC16A3, which correlated with poor disease-free survival. Our study reveals a previously unrecognized EGF-secretory autophagy axis that orchestrates metabolic remodeling in TNBC and highlights the therapeutic potential of targeting the secretory autophagy- SLC16A3-lactate pathway to restrain metastasis.
    Keywords:  Lactate secretion; SLC16A3/MCT4; TNBC; metastasis; secretory autophagy; tumor microenvironment
    DOI:  https://doi.org/10.1080/15548627.2026.2656780
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