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This study reveals an adaptive mechanism that harnesses synergistic paracrine signalling via IL-6\/8, which is amplified by cell proliferation and cell density, to directly promote cell migration. This effect occurs in metastatic human sarcoma and carcinoma cells\u2013 but not in normal or non-metastatic cancer cells-, and likely involves the downstream signalling of WASF3 and Arp2\/3. The transcriptional phenotype of high-density cells that emerges due to proliferation resembles that of low-density cells treated with a combination of IL-6\/8. Simultaneous inhibition of IL-6\/8 receptors decreases the expression of WASF3 and Arp2\/3 in a mouse xenograft model and reduces metastasis. This study reveals a potential mechanism that promotes tumour cell migration and infers a strategy to decrease metastatic capacity of tumour cells.<\/jats:p>","DOI":"10.1038\/ncomms15584","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T06:21:49Z","timestamp":1495779709000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["Synergistic IL-6 and IL-8 paracrine signalling pathway infers a strategy to inhibit tumour cell migration"],"prefix":"10.1038","volume":"8","author":[{"given":"Hasini","family":"Jayatilaka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6848-4900","authenticated-orcid":false,"given":"Pranay","family":"Tyle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan J.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsuk","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Ju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Ji","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry S. 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