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

Jäntti, N. Z.; Moreno-Layseca, P.; Chastney, M. R.; Dibus, M.; Conway, J. R. W.; Leppänen, V.-M.; Hamidi, H.; Eylmann, K.; Oliveira-Ferrer, L.; Veltel, S.; Ivaska, J.

doi:10.1101/2024.06.27.600789

bioRxiv · 10.1101/2024.06.27.600789

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

Jäntti, N. Z.·Moreno-Layseca, P.·Chastney, M. R.·Dibus, M.·Conway, J. R. W.·Leppänen, V.-M.·Hamidi, H.·Eylmann, K.·Oliveira-Ferrer, L.·Veltel, S.·Ivaska, J.

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Abstract

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

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Jäntti, N. Z., Moreno-Layseca, P., Chastney, M. R., Dibus, M., Conway, J. R. W., Leppänen, V.-M., Hamidi, H., Eylmann, K., Oliveira-Ferrer, L., Veltel, S., Ivaska, J.. 2024-06-28. EPLINα controls integrin recycling from Rab21 endosomes to drive breast cancer cell migration. https://doi.org/10.1101/2024.06.27.600789

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