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 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 traffic. 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 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Mammary Gland Epithelial Cell

DISEASE(S): Breast Cancer

SUBMITTER: Megan Chastney  

LAB HEAD: Johanna Ivaska

PROVIDER: PXD052819 | Pride | 2025-08-26

REPOSITORIES: Pride