EPLINα controls integrin recycling from Rab21 endosomes to drive breast cancer cell migration

Abstract

EPLIN, an actin-binding protein, has been described as both a tumour promoter and tumour suppressor in different cancers. EPLIN isoform(α or β)-specific functions, which remain largely unknown, could explain these opposing roles. We observed distinct EPLIN-isoform localization; EPLINα is recruited to actin in plasma membrane ruffles and endosomes, while EPLINβ resides on actin stress fibers. We identified two EPLIN actin-binding regions and demonstrated EPLINα interaction with Rab21, an established regulator of β1-integrin endosomal traffic. EPLINα co-localizes with Rab21 and F-actin on recycling endosomes in an actin binding-dependent manner and supports β1-integrin recycling and cell migration. Using BioID, we identified coronin 1C as an EPLIN proximal protein, which localizes at Rab21-containing endosomes in an EPLINα-dependent manner. EPLINα expression was linked to increased breast cancer cell motility, and high EPLINα-to-EPLINβ ratio correlated with a mesenchymal phenotype in patient samples. Our work unveils unprecedented EPLIN isoform-specific functions relevant to breast cancer and beyond.