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

// Chen-Hung Ting 1 , Yi-Chun Chen 1 , Chang-Jer Wu 2 , Jyh-Yih Chen 1 1 Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, Jiaushi, Ilan 262, Taiwan 2 Department of Food Science, National Taiwan Ocean University, Keelung 202, Taiwan Correspondence to: Jyh-Yih Chen, email: zoocjy@gate.sinica.edu.tw Keywords: TP4, cationic antimicrobial peptide, triple-negative breast cancer, calcium, FOSB Received: February 12, 2016 Accepted: May 02, 2016 Published: May 26, 2016 ABSTRACT 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.