Mitochondrial Reprogramming Regulated Cancer Pathway In Triple Negative Breast Cancer

Compared to other subtypes of tumors, triple negative breast cancers (TN BCa) currently suffer from limited knowledge on its etiology and treatment options. Transmitochondrial cybrids (cybrid) and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in TN BCa. Analysis of cybrids and established BCa cell lines showed that metastatic TN BCa maintain high levels of ATP through fatty acid β-oxidation and activate Src oncoprotein by its autophosphorylation. Inhibition and induction of β-oxidation including the shRNA mediated knockdown strategies, and analysis of patient derived xenograft (PDX) models confirmed the role of mitochondrial β-oxidation in Src activation and metastasis. Analysis of BCa clinical data further reaffirmed the role of mitochondrial β-oxidation in Src regulation and their significance in BCa metastasis. This study is innovative in showing the mitochondrial reprogramming mediated regulation of a major cancer pathway by its post-translation modification. Citation Format: Jun H. Park, Sajna Vithayathil, Danli Wu, Vasanta Putluri, Pi-Lin Sung, Efrosini Tsouko, Vadiraja B. Bhat, Cristian Coarfa, Daniel E. Frigo, Michael T. Lewis, Arun Sreekumar, Patricia Yotnda, Chad J. Creighton, Nagireddy Putluri, Lee-Jun C. Wong, Benny A. Kaipparettu. Mitochondrial reprogramming regulated cancer pathway in triple negative breast cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 217.