IL-17A and its homologs IL-25/IL-17E recruit the c-RAF/S6 kinase pathway and the generation of pro-oncogenic LMW-E in breast cancer cells

Sarah Mombelli 1, 2, 3 Stéphanie Cochaud Yacine Merrouche 3 Christian Garbar 3 Frank Antonicelli 3 Emilie Laprevotte 4 Gilles Alberici Nathalie Bonnefoy 4 Jean-François Eliaou 4, 5 Jérémy Bastid Armand Bensussan Jérôme Giustiniani 3
1 IDO (U976 / UMR_S 976) - Immunologie, dermatologie, oncologie ; Oncodermatologie, immunologie et cellules souches cutanées
2 Institut Jean Godinot
3 ICA - Immunodermatologie, Cytokines, Cancer - EA 7319
4 IRCM - U1194 Inserm - UM - Institut de Recherche en Cancérologie de Montpellier
5 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
Abstract : Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we report that IL-17A and IL-17E receptors subunits mRNA expressions are upregulated in breast cancers versus normal samples. IL-17E, which is undetectable in most normal breast tissues tested, seems more expressed in some tumors. Investigation of the molecular signaling following stimulation of human breast cancer cell lines with IL-17A and IL-17E showed that both cytokines induced the phosphorylation of c-RAF, ERK1/2 and p70 S6 Kinase were involved in the proliferation and survival of tumor cells. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel and failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorogenic low molecular weight forms of cyclin E (LMW-E), which high levels correlated strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers.
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Sarah Mombelli, Stéphanie Cochaud, Yacine Merrouche, Christian Garbar, Frank Antonicelli, et al.. IL-17A and its homologs IL-25/IL-17E recruit the c-RAF/S6 kinase pathway and the generation of pro-oncogenic LMW-E in breast cancer cells. Scientific Reports, Nature Publishing Group, 2015, 5 (1), pp.11874. ⟨10.1038/srep11874⟩. ⟨hal-01841216⟩

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