The IL-17B-IL-17 receptor B pathway promotes resistance to paclitaxel in breast tumors through activation of the ERK1/2 pathway.
Fiche publication
Date publication
décembre 2017
Journal
Oncotarget
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BENSUSSAN Armand
Tous les auteurs :
Laprevotte E, Cochaud S, du Manoir S, Lapierre M, Dejou C, Philippe M, Giustiniani J, Frewer KA, Sanders AJ, Jiang WG, Michaud HA, Colombo PE, Bensussan A, Alberici G, Bastid J, Eliaou JF, Bonnefoy N
Lien Pubmed
Résumé
Interleukin 17B (IL-17B) is a pro-inflammatory cytokine that belongs to the IL-17 cytokines family and binds to IL-17 receptor B (IL-17RB). Here we found that high expression of IL-17B and IL-17RB is associated with poor prognosis in patients with breast cancer and that IL-17B expression upregulation is specifically associated with poorer survival in patients with basal-like breast cancer. We thus focused on IL-17B role in breast cancer by using luminal and triple negative (TN)/basal-like tumor cell lines. We found that IL-17B induces resistance to conventional chemotherapeutic agents. , IL-17B induced resistance to paclitaxel and treatment with an anti-IL-17RB neutralizing antibody completely restored breast tumor chemosensitivity, leading to tumor shrinkage. We next focused on the signaling pathways activated in human breast cancer cell lines upon incubation with IL-17B. We observed that IL-17B induces ERK1/2 pathway activation, leading to upregulation of anti-apoptotic proteins of the BCL-2 family. IL-17B-induced chemoresistance was completely abolished by incubation with PD98059, an inhibitor of the MAPK/ERK pathway, indicating that the ERK pathway plays a crucial role. Altogether our results emphasize the role of the IL-17B/IL-17RB signaling pathway in breast tumors and identify IL-17B and its receptor as attractive therapeutic targets for potentiating breast cancer chemotherapy.
Mots clés
breast cancer, chemoresistance, interleukin-17, interleukin-17B, paclitaxel
Référence
Oncotarget. 2017 12 26;8(69):113360-113372