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Targeting FOSB with a cationic antimicrobial peptide, TP4, for treatment of triple-negative breast cancer

Oncotarget, DOI: 10.18632/oncotarget.9612

http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=9612

Triple-negative breast cancer (TNBC) currently lacks a suitable therapeutic candidate and is thus difficult to treat. Here, we report that a cationic antimicrobial peptide (CAP), tilapia piscidin 4 (TP4), which was derived from Nile tilapia (Oreochromis niloticus), is selectively toxic to TNBC. TP4 acts by inducing an AP-1 protein called FOSB, the expression of which is negatively associated with the pathological grade of TNBC. We show that TP4 is bound to the mitochondria where it disrupts calcium homeostasis and activates FOSB. FOSB overexpression results in TNBC cell death, whereas inhibition of calcium signaling eliminates FOSB induction and blocks TP4-induced TNBC cell death. Both TP4 and anthracyclines strongly induced FOSB, particularly in TNBC, indicating that FOSB may be suitable as a biomarker of drug responses. This study thus provides a novel therapeutic approach toward TNBC through FOSB induction.

 

 


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115台北市南港區研究院路二段128號
Tel: 02-27899515
Fax: 02-27858059
icob@gate.sinica.edu.tw
Copyright © ICOB 2013. All rights reserved. 最佳瀏覽網頁方式請用最新版IE11或其他瀏覽器 /瀏覽人數:1594460--
 瀏覽人數:1594460