Auto-antibodies against apolipoprotein a-1 block cancer cells proliferation and induce apoptosis

Article Article scientifique Article Auto-antibodies against apolipoprotein a-1 block cancer cells proliferation and induce apoptosis eng 2020-11-17 2020-11-17 author Satta Poschung Nathalie 134524 author Weppe Rémy 862311 author Pagano Sabrina 0000-0001-7075-1182 758239 author Frias Miguel 0000-0001-6884-4793 502571 author Juillard Mochon Catherine 26802 author Vuilleumier Nicolas 61406 4266-4280 10.18632/oncotarget.27814 33245719 1949-2553 PMC7679029 https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.27814 Auto-antibodies against apoA-1 (anti-apoA-1 IgGs) have been identified as important actors of atherosclerosis development through pro-inflammatory and pro-atherogenic properties and to also induce apoptosis in tumoral neuronal and lymphocyte derived cell lines through unknown mechanisms. The purpose of this study was to explore the cellular pathways involved in tumoral cell survival modulated by anti-apoA-1 antibodies. We observed that anti-apoA-1 antibodies induce growth arrest (in G2/M phase) and cell apoptosis through caspase 3 activation, accompanied by a selective p53 phosphorylation on serine 15. RNA sequencing indicated that anti-apoA-1 IgGs affect the expression of more than 950 genes belonging to five major groups of genes and respectively involved in i) cell proliferation inhibition, ii) p53 stabilisation and regulation, iii) apoptosis regulation, iv) inflammation regulation, and v) oxidative stress. In conclusion, anti-apoA-1 antibodies seem to have a role in blocking tumoral cell proliferation and survival, by activating a major tumor suppressor protein and by modulating the inflammatory and oxidative stress response. Further investigations are needed to explore a possible anti-cancer therapeutic approach of these antibodies in very specific and circumscribed conditions. Anti-apoA-1 antibodies Apoptose Cell proliferation Oxidative stress Dewey 616 Swiss National Science Foundation Human autoantibody response to the C-terminal helix of apolipoprotein A-1 as new rationale for prognosis and treatment of cardiovascular disease 163335 CH Project funding Leenards Foundation 3698 56 Département de médecine 221 false 211 Auto-immunité, inflammation et athérosclérose 270 Oncotarget 11 46 6f86c873-a2be-4631-80ee-28305755543e Article (Published version) Public Article-scientifique-from-unpaywall.pdf 3362367 application/pdf CC BY-3.0 openAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Auto-antibodies against apolipoprotein a-1 block cancer cells proliferation and induce apoptosis	Oncotarget			2020	168	115

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Weppe, Rémy