2025/07/16 by Niklas Z. Jäntti, Paulina Moreno‐Layseca, Megan Chastney +8 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · Medicine · #Cell Adhesion Molecules Research #Cellular transport and secretion #Protease and Inhibitor Mechanisms
paper · doi:10.1016/j.devcel.2025.06.025
openalex publication_date 2025/07/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/22
Epithelial protein lost in neoplasm (EPLIN), an actin-binding protein, has been described as both a tumor promoter and tumor suppressor in different cancers. The roles of EPLIN isoforms (α/β) remain largely unknown and could explain these opposing views. We observed distinct EPLIN isoform localization in breast cancer cells; EPLINα is recruited to actin in plasma membrane ruffles and endosomes, while EPLINβ resides on stress fibers. EPLINα localizes to early endosomes in an actin-dependent manner, where it interacts with Rab21, an established regulator of β1-integrin endosomal trafficking. This supports β1-integrin recycling and cell migration. Using proximity biotinylation (BioID), we identified coronin 1C as an EPLIN-proximal protein, which also localizes at Rab21-containing endosomes and controls integrin recycling downstream of EPLINα. EPLINα expression was linked to increased breast cancer cell motility, and a high EPLINα-to-EPLINβ ratio correlated with a mesenchymal phenotype in patient samples. Our work identifies previously unknown EPLIN-isoform-specific functions relevant to breast cancer and beyond.