{"doi":"10.1111/febs.16046","title":"The gate to metastasis: key players in cancer cell intravasation","abstract":"<jats:p>Metastasis is a leading cause of cancer‐related death and consists of a sequence of events including tumor expansion, intravasation of cancer cells into the circulation, survival in the bloodstream, extravasation at distant sites, and subsequent organ colonization. Particularly, intravasation is a process whereby cancer cells transverse the endothelium and leave the primary tumor site, pioneering the metastatic cascade. The identification of those mechanisms that trigger the entry of cancer cells into the bloodstream may reveal fundamentally novel ways to block metastasis at its start. Multiple factors have been implicated in cancer progression, yet, signals that unequivocally provoke the detachment of cancer cells from the primary tumor are still under investigation. Here, we discuss the role of intrinsic properties of cancer cells, tumor microenvironment, and mechanical cues in the intravasation process, outlining studies that suggest the involvement of various factors and highlighting current understanding and open questions in the field.</jats:p>","journal":"The FEBS Journal","year":2022,"id":634973,"datarank":0.6515708132780527,"base_score":4.343805421853684,"endowment":4.343805421853684,"self_citation_contribution":0.6515708132780527,"citation_network_contribution":0.0,"self_endowment_contribution":0.6515708132780527,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":76,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":230838,"name":"Nicola Aceto","orcid":"0000-0001-9579-6918","position":1,"is_corresponding":false},{"id":637723,"name":"Magdalena K. Sznurkowska","orcid":"0000-0001-5306-2385","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"The gate to metastasis: key players in cancer cell intravasation","abstract":"<jats:p>Metastasis is a leading cause of cancer‐related death and consists of a sequence of events including tumor expansion, intravasation of cancer cells into the circulation, survival in the bloodstream, extravasation at distant sites, and subsequent organ colonization. Particularly, intravasation is a process whereby cancer cells transverse the endothelium and leave the primary tumor site, pioneering the metastatic cascade. The identification of those mechanisms that trigger the entry of cancer cells into the bloodstream may reveal fundamentally novel ways to block metastasis at its start. Multiple factors have been implicated in cancer progression, yet, signals that unequivocally provoke the detachment of cancer cells from the primary tumor are still under investigation. Here, we discuss the role of intrinsic properties of cancer cells, tumor microenvironment, and mechanical cues in the intravasation process, outlining studies that suggest the involvement of various factors and highlighting current understanding and open questions in the field.</jats:p>","is_dataset_classified":null,"base_score":4.343805421853684,"endowment":4.343805421853684,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34077633","pmcid":"PMC9546053","openalex_id":"https://openalex.org/W3165405072","authors":[],"funders":[{"funder_name":"European Research Council","grant_id":"678834","title":"Holding hands: cell-cell junctions in breast cancer metastasis and resistance to therapy"},{"funder_name":"Swiss National Science Foundation","grant_id":"163938","title":"Discovery of fundamental mechanisms underlying the development of cancer metastasis"},{"funder_name":"European Research Council","grant_id":"840636","title":"Development of small molecule inhibitors of circulating tumor cell clusters"},{"funder_name":"European Commission","grant_id":"847012","title":"Unravelling the molecular and cellular mechanism of metastasis"},{"funder_name":"Swiss National Science Foundation","grant_id":"182962","title":"Exploiting Small Molecules to Unravel Vulnerabilities of Circulating Tumor Cells"},{"funder_name":"Swiss National Science Foundation","grant_id":"190077","title":"Discovery of fundamental mechanisms underlying the development of cancer metastasis"},{"funder_name":"European Commission","grant_id":"801159","title":"Modeling spontaneous Breast cancer metastasis TO the Bone with a first-of-its-kind 3D device that recapitulates physiological tissue-level complexity."},{"funder_name":"Krebsliga Schweiz","grant_id":"","title":null},{"funder_name":"European Research Council","grant_id":"","title":null},{"funder_name":"Swiss National Science Foundation","grant_id":"","title":null},{"funder_name":"Krebsliga Beider Basel","grant_id":"","title":null},{"funder_name":"H2020 Future and Emerging Technologies","grant_id":"","title":null}],"total_grants":12,"fwci":3.9728,"citation_percentile":0.96066149,"influential_citations":0,"citation_trend":[{"year":2021,"count":4},{"year":2022,"count":10},{"year":2023,"count":16},{"year":2024,"count":19},{"year":2025,"count":14},{"year":2026,"count":13}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/febs.16046","host_type":"journal"},{"url":"https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/febs.16046","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/febs.16046","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/full-xml/10.1111/febs.16046","host_type":"publisher"},{"url":"https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/febs.16046","host_type":"publisher"},{"url":"https://doi.org/10.1111/febs.16046","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34077633","host_type":"repository"},{"url":"http://hdl.handle.net/20.500.11850/494757","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9546053","host_type":"repository"},{"url":"https://doi.org/10.3929/ethz-b-000494757","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9546053","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9546053?pdf=render","host_type":"Europe_PMC"},{"url":"https://dx.doi.org/10.3929/ethz-b-000494757","host_type":""},{"url":"http://dx.doi.org/10.1111/febs.16046","host_type":""},{"url":"https://dx.doi.org/10.1111/febs.16046","host_type":""}],"fields_of_study":["Cancer Cells and Metastasis","Angiogenesis and VEGF in Cancer","Cancer, Hypoxia, and Metabolism","0301 basic medicine","03 medical and health sciences","Humans","Neoplasm Metastasis","Neoplasms","Tumor Microenvironment"],"mesh_terms":["Humans","Neoplasm Metastasis","Neoplasms","Tumor Microenvironment"],"keywords":["Intravasation","Extravasation","Metastasis","Cancer","Cancer cell","Cancer research","Primary tumor","Biology","Tumor microenvironment","Medicine","Immunology","Genetics","Circulating Tumor Cells","State‐of‐the‐Art Reviews","Neoplasms","cancer; circulating tumor cells; intravasation; metastasis","Humans","Neoplasm Metastasis"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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