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 l Show more
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. Show less
Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-in Show more
Spatially controlled, cargo-specific endocytosis is essential for development, tissue homeostasis and cancer invasion. Unlike cargo-specific clathrin-mediated endocytosis, the clathrin- and dynamin-independent endocytic pathway (CLIC-GEEC, CG pathway) is considered a bulk internalization route for the fluid phase, glycosylated membrane proteins and lipids. While the core molecular players of CG-endocytosis have been recently defined, evidence of cargo-specific adaptors or selective uptake of proteins for the pathway are lacking. Here we identify the actin-binding protein Swiprosin-1 (Swip1, EFHD2) as a cargo-specific adaptor for CG-endocytosis. Swip1 couples active Rab21-associated integrins with key components of the CG-endocytic machinery-Arf1, IRSp53 and actin-and is critical for integrin endocytosis. Through this function, Swip1 supports integrin-dependent cancer-cell migration and invasion, and is a negative prognostic marker in breast cancer. Our results demonstrate a previously unknown cargo selectivity for the CG pathway and a role for specific adaptors in recruitment into this endocytic route. Show less