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CLICing on endocytic cargoes for cancer invasion

Nature Cell Biology volume 23, pages 1052–1053 (2021)Cite this article

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Clathrin- and dynamin-independent endocytosis is considered a major ‘default’ uptake route for cells, but a recent study describes the selective recruitment of integrin-adhesion receptor cargoes via the endocytic adaptor Swip1, which promotes breast cancer invasion and metastasis.

Although some routes of endocytosis are well characterized, other important pathways have remained enigmatic. For example, clathrin-independent carriers (CLICs) are a major route of uptake for fluid-phase, glycosylphosphatidylinositol-anchored proteins (GPI-APs), and lipids. These cargos are internalised in a dynamin-independent fashion and are routed to GPI-AP-enriched early endosomal compartments (GEECs)1. How cargoes might be selected for the CLIC–GEEC (CG) pathway was unclear. By studying the endocytosis of integrins driven by the small GTPase Rab21, Moreno-Layseca et al. found that a critical adaptor, Swiprosin-1 (Swip1), interacted directly with Rab21–integrin complexes to recruit them to the CG pathway for endocytosis2. Through its actin-binding ability, Swip1 also controlled F-actin-mediated transport of Rab21–integrin vesicles and regulated the turnover of cell-matrix adhesion complexes to promote breast cancer invasion and metastasis. This work reveals a previously unknown facet of the CG pathway — the ability to selectively recruit cargoes — and raises the possibility that other cargoes could be recruited via related mechanisms. This study further affirms the links between endocytosis, integrin trafficking and metastasis, and provides a new focus for therapeutic strategies to help improve prognoses in cancer.

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Fig. 1: SWIP1 is a β1 integrin–specific cargo adaptor for the CG pathway.

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  1. Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, Faculty of Biology Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester, UK

    Patrick T. Caswell

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Correspondence to Patrick T. Caswell.

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Caswell, P.T. CLICing on endocytic cargoes for cancer invasion. Nat Cell Biol 23, 1052–1053 (2021). https://doi.org/10.1038/s41556-021-00763-1

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