A1 Refereed original research article in a scientific journal
EPLINα controls integrin recycling from Rab21 endosomes to drive breast cancer cell migration
Authors: Jäntti, Niklas Z.; Moreno-Layseca, Paulina; Chastney, Megan R.; Dibus, Michal; Conway, James R.W.; Leppänen, Veli-Matti; Hamidi, Hellyeh; Eylmann, Kathrin; Oliveira-Ferrer, Leticia; Veltel, Stefan; Ivaska, Johanna
Publisher: Elsevier BV
Publication year: 2025
Journal: Developmental Cell
Journal name in source: Developmental Cell
ISSN: 1534-5807
DOI: https://doi.org/10.1016/j.devcel.2025.06.025
Web address : https://doi.org/10.1016/j.devcel.2025.06.025
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/499492863
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.
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Funding information in the publication:
We thank P. Laasola and J. Siivonen for technical assistance and the Ivaska laboratory for critical reading of the manuscript and constructive feedback. We thank James Bear (University of North Carolina-Chapel Hill School of Medicine, Chapel Hill, North Carolina, USA) for providing reagents. The Cell Imaging and cytometry core (Turku Bioscience Centre, University of Turku and Åbo Akademi University and Biocenter Finland) are acknowledged for services, instrumentation, and expertise. We also thank Christoffer Lagerholm for assistance with image acquisition. This work was supported by the Finnish Cancer Institute (K. Albin Johansson Professorship to J.I.), a Research Council of
Finland project grant (#325464 to J.I.) and Centre of Excellence program (#346131 to J.I.), the Cancer Foundation Finland (J.I.), the Sigrid Juselius Foundation (J.I.), the Research Council of Finland’s Flagship InFLAMES (#337530 and 357910), the Jane and Aatos Erkko Foundation (J.I.), and European Research Council advanced grant (#101142305; Border Control). N.Z.J. was supported by the University of Turku Doctoral Programme in Technology, the Swedish Cultural Foundation in Finland, the Varsinais-Suomi Regional Fund, the K. Albin Johansson Foundation, and the Ida Montin Foundation. This study has been supported by the Research Council of Finland postdoctoral fellowships (grant nos. 321493 [to P.M.-L.], 338585 [to J.R.W.C], and 343239 [to M.R.C.]) and Research Fellowship (grant no. 360775 to J.R.W.C). J.R.W.C. was also supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement (grant 841973). M.D. was supported by the European Union’s Horizon Europe research and innovation programme under Marie Sklodowska-Curie grant agreement no. 101108089.
