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 ORCID: https://orcid.org/0000-0002-7997-5286, Jiang, Wen ORCID: https://orcid.org/0000-0002-3283-1111, 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:	05 May 2023 08:33
URI:	https://orca.cardiff.ac.uk/id/eprint/107578

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