Cell Reports (Mar 2016)
Fatty Acid Oxidation-Driven Src Links Mitochondrial Energy Reprogramming and Oncogenic Properties in Triple-Negative Breast Cancer
- Jun Hyoung Park,
- Sajna Vithayathil,
- Santosh Kumar,
- Pi-Lin Sung,
- Lacey Elizabeth Dobrolecki,
- Vasanta Putluri,
- Vadiraja B. Bhat,
- Salil Kumar Bhowmik,
- Vineet Gupta,
- Kavisha Arora,
- Danli Wu,
- Efrosini Tsouko,
- Yiqun Zhang,
- Suman Maity,
- Taraka R. Donti,
- Brett H. Graham,
- Daniel E. Frigo,
- Cristian Coarfa,
- Patricia Yotnda,
- Nagireddy Putluri,
- Arun Sreekumar,
- Michael T. Lewis,
- Chad J. Creighton,
- Lee-Jun C. Wong,
- Benny Abraham Kaipparettu
Affiliations
- Jun Hyoung Park
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Sajna Vithayathil
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Santosh Kumar
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Pi-Lin Sung
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Lacey Elizabeth Dobrolecki
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Vasanta Putluri
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
- Vadiraja B. Bhat
- Agilent Technologies, Wilmington, DE 19808, USA
- Salil Kumar Bhowmik
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
- Vineet Gupta
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Kavisha Arora
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Danli Wu
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
- Efrosini Tsouko
- Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
- Yiqun Zhang
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Suman Maity
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
- Taraka R. Donti
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Brett H. Graham
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Daniel E. Frigo
- Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
- Cristian Coarfa
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
- Patricia Yotnda
- Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA
- Nagireddy Putluri
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
- Arun Sreekumar
- Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
- Michael T. Lewis
- Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX 77030, USA
- Chad J. Creighton
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA
- Lee-Jun C. Wong
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- Benny Abraham Kaipparettu
- Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
- DOI
- https://doi.org/10.1016/j.celrep.2016.02.004
- Journal volume & issue
-
Vol. 14,
no. 9
pp. 2154 – 2165
Abstract
Transmitochondrial cybrids and multiple OMICs approaches were used to understand mitochondrial reprogramming and mitochondria-regulated cancer pathways in triple-negative breast cancer (TNBC). Analysis of cybrids and established breast cancer (BC) cell lines showed that metastatic TNBC maintains high levels of ATP through fatty acid β oxidation (FAO) and activates Src oncoprotein through autophosphorylation at Y419. Manipulation of FAO including the knocking down of carnitine palmitoyltransferase-1A (CPT1) and 2 (CPT2), the rate-limiting proteins of FAO, and analysis of patient-derived xenograft models confirmed the role of mitochondrial FAO in Src activation and metastasis. Analysis of TCGA and other independent BC clinical data further reaffirmed the role of mitochondrial FAO and CPT genes in Src regulation and their significance in BC metastasis.
