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In the present study we show that a multi-purpose drug suramin inhibits Wnt signalling and proliferation of TNBC cells in\u00a0vitro and in mouse models, inhibiting a component in the upper levels of the pathway. Through a set of investigations we identify heterotrimeric G proteins and regulation of Wnt endocytosis as the likely target of suramin in this pathway. G protein-dependent endocytosis of plasma membrane-located components of the Wnt pathway was previously shown to be important for amplification of the signal in this cascade. Our data identify endocytic regulation within Wnt signalling as a promising target for anti-Wnt and anti-cancer drug discovery. Suramin, as the first example of such drug or its analogues might pave the way for the appearance of first-in-class targeted therapies against TNBC and other Wnt-dependent cancers.<\/jats:p>","DOI":"10.1042\/bj20150913","type":"journal-article","created":{"date-parts":[[2015,11,25]],"date-time":"2015-11-25T02:12:53Z","timestamp":1448417573000},"page":"371-381","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Inhibition of Wnt signalling and breast tumour growth by the multi-purpose drug suramin through suppression of heterotrimeric G proteins and Wnt endocytosis"],"prefix":"10.1042","volume":"473","author":[{"given":"Alexey","family":"Koval","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Lausanne, Lausanne 1011, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamal","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Lausanne, Lausanne 1011, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir\u00a0L.","family":"Katanaev","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, University of Lausanne, Lausanne 1011, Switzerland"},{"name":"School of Biomedicine, Far Eastern Federal University, Vladivostok 690950, Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,2,9]]},"reference":[{"key":"2021112216341752200_B1","first-page":"675","article-title":"Sur une nouvelle s\u00e9rie de m\u00e9dicaments trypanocides","volume":"178","author":"Fourneau","year":"1924","journal-title":"Comptes Rendus S\u00e9ances Acad\u00e9mie Sci."},{"key":"2021112216341752200_B2","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1038\/sj.bjp.0707354","article-title":"Human African trypanosomiasis: pharmacological re-engagement with a neglected disease","volume":"152","author":"Barrett","year":"2007","journal-title":"Br. 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