Cancer metastasis is a complex, multi-step process that accounts for the majority of cancer-related deaths. Cell motility and directional migration are central to these processes. Cell migration’s molecular mechanisms and metastatic disease progression are strongly correlated, and Caveolin-1 (CAV1) is expected to be involved in metastasis based on its role in migrating cells. In early-stage cancers, CAV1 typically suppresses tumour growth by inhibiting cell proliferation and stabilising cellular signalling, and its downregulation or loss is commonly linked to tumour initiation. However, in advanced cancers, CAV1 expression is often upregulated and facilitates tumour progression by enhancing cell migration, invasion, metastasis, and resistance to therapy. Consequently, CAV1 has emerged as a critical mediator in transitioning from localised tumour growth to metastatic spread. However, the context-dependent roles of CAV1 make it difficult to understand its role in metastasis. This review aims to provide a comprehensive overview of the involvement of CAV1 in different modes of cancer cell migration and metastasis. We discuss its molecular functions, context-dependent roles, and interactions with key signalling pathways, including extracellular vesicle signalling, that control cell movement, shedding light on its complex contribution to cancer progression.

Department of Biochemistry and Molecular Biology Faculty of Medicine The Institute for Medical Research Israel Canada Hebrew University of Jerusalem Jerusalem Israel

Department of Pathological Physiology Faculty of Medicine Masaryk University Kamenice 5 Brno CZ 625 00 Czech Republic

Department of Physiology Faculty of Medicine Masaryk University Kamenice 5 Brno CZ 625 00 Czech Republic

Institute of Pathophysiology 1st Faculty of Medicine Charles University U Nemocnice 5 Prague CZ 128 53 Czech Republic

International Clinical Research Center St Anne's University Hospital Brno 60200 Czech Republic

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