Data from Aurora A and NF-κB Survival Pathway Drive Chemoresistance in Acute Myeloid Leukemia via the TRAF-Interacting Protein TIFA

التفاصيل البيبلوغرافية
العنوان: Data from Aurora A and NF-κB Survival Pathway Drive Chemoresistance in Acute Myeloid Leukemia via the TRAF-Interacting Protein TIFA
المؤلفون: Ming-Daw Tsai, Hwei-Fang Tien, Shih-Lan Hsu, Chang-Tze Ricky Yu, Chia-Chi Flora Huang, Hsiang-Chun Su, Ting-Yang Lin, Jo-Mei Maureen Chen, Chih-Ru Lin, Chieh-Lin Jerry Teng, Wen-Chien Chou, Hsin-An Hou, Ting-Jung Wu, Pei-Yu Wu, Tong-You Wade Wei
بيانات النشر: American Association for Cancer Research (AACR), 2023.
سنة النشر: 2023
الوصف: Aurora A–dependent NF-κB signaling portends poor prognosis in acute myeloid leukemia (AML) and other cancers, but the functional basis underlying this association is unclear. Here, we report that Aurora A is essential for Thr9 phosphorylation of the TRAF-interacting protein TIFA, triggering activation of the NF-κB survival pathway in AML. TIFA protein was overexpressed concurrently with Aurora A and NF-κB signaling factors in patients with de novo AML relative to healthy individuals and also correlated with poor prognosis. Silencing TIFA in AML lines and primary patient cells decreased leukemic cell growth and chemoresistance via downregulation of prosurvival factors Bcl-2 and Bcl-XL that support NF-κB–dependent antiapoptotic events. Inhibiting TIFA perturbed leukemic cytokine secretion and reduced the IC50 of chemotherapeutic drug treatments in AML cells. Furthermore, in vivo delivery of TIFA-inhibitory fragments potentiated the clearance of myeloblasts in the bone marrow of xenograft-recipient mice via enhanced chemotoxicity. Collectively, our results showed that TIFA supports AML progression and that its targeting can enhance the efficacy of AML treatments. Cancer Res; 77(2); 494–508. ©2016 AACR.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8aafe8ebf0d3ec42743e57bfca870885
https://doi.org/10.1158/0008-5472.c.6508910
حقوق: OPEN
رقم الأكسشن: edsair.doi.dedup.....8aafe8ebf0d3ec42743e57bfca870885
قاعدة البيانات: OpenAIRE