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The IL-17B-IL-17 receptor B pathway promotes resistance to paclitaxel in breast tumors through activation of the ERK1/2 pathway

Laprevotte, Emilie, Cochaud, Stéphanie, Manoir, Stanislas du, Lapierre, Marion, Dejou, Cécile, Philippe, Marion, Giustiniani, Jérome, Frewer, Kathryn, Sanders, Andrew, Jiang, Wen, Michaud, Henri-Alexandre, Colombo, Pierre-Emmanuel, Bensussan, Armand, Alberici, Gilles, Bastid, Jérémy, Eliaou, Jean-François and Bonnefoy, Nathalie 2017. The IL-17B-IL-17 receptor B pathway promotes resistance to paclitaxel in breast tumors through activation of the ERK1/2 pathway. Oncotarget 8 , pp. 113360-113372. 10.18632/oncotarget.23008

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Abstract

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. In vivo, 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: Impact Journals LLC
ISSN: 1949-2553
Funders: Cancer Research Wales, Life Sciences Research Network Wales (Welsh Government's Ser Cymru program), Albert Huang Foundation, Cardiff China Medical Scholarship
Date of First Compliant Deposit: 22 December 2017
Date of Acceptance: 13 November 2017
Last Modified: 04 Jan 2018 14:31
URI: http://orca.cf.ac.uk/id/eprint/107578

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