title: Mitochondrial Reprogramming Regulates Breast Cancer Progression.
abstract: The goal of this study was to understand the role of altered mitochondrial function in breast cancer progression and determine the potential of the molecular alteration signature in developing exosome-based biomarkers.
  
  
  
  This study was designed to characterize the critical components regulating mitochondrial function in breast tumorigenesis. Experiments were conducted to assess the potential of these molecules for exosome-based biomarker development.
  
  
  
  We observed a remarkable reduction in spontaneous metastases through the interplay in mitochondria by SH3GL2, vesicular endocytosis-associated protein and MFN2, an important regulator of mitochondrial fusion. Following its overexpression in breast cancer cells, SH3GL2 translocated to mitochondria and induced the production of superoxide and release of cytochrome C from mitochondria to the cytoplasm. These molecular changes were accompanied by decreased lung and liver metastases and primary tumor growth. SH3GL2 depletion reversed the above phenotypic and associated molecular changes in nontumorigenic and tumorigenic breast epithelial cells. Loss of SH3GL2 and MFN2 expression was evident in primary human breast cancer tissues and their positive lymph nodes, which was associated with disease progression. SH3GL2 and MFN2 expression was detected in sera exosomes of normal healthy women, but barely detectable in the majority of the women with breast cancer exhibiting SH3GL2 and MFN2 loss in their primary tumors.
  
  
  
  This study identified a new mitochondria reprogramming pathway influencing breast cancer progression through SH3GL2 and MFN2. These proteins were frequently lost in breast cancer, which was traceable in the circulating exosomes. Clin Cancer Res; 22(13); 3348-60. ©2016 AACR.
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Kannan
authors.affiliation: Department of Pathology, The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Wells
authors.affiliation: Department of Biochemistry, Sri Sankara Arts and Science College, Kanchipuram, Tamil Nadu, India.
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Sivakumar
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: University of Alabama at Birmingham Comprehensive Cancer Center's Biostatistics and Bioinformatics Shared Facility, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Karan P
authors.initials: KP
authors.lastname: Singh
authors.affiliation: Department of Microbiology and Immunology, The University of Texas Health Science Center, Tyler, Texas.
authors.forename: Buka
authors.initials: B
authors.lastname: Samten
authors.affiliation: Department of Medicine, The University of Texas Health Science Center, Tyler, Texas.
authors.forename: Julie V
authors.initials: JV
authors.lastname: Philley
authors.affiliation: Department of Surgery, The University of Texas Health Science Center, Tyler, Texas.
authors.forename: Edward R
authors.initials: ER
authors.lastname: Sauter
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas.
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Ikebe
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas. The Texas Lung Injury Institute, The University of Texas Health Science Center, Tyler, Texas.
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
authors.affiliation: Department of Medical Oncology, Tata Memorial Center, Mumbai, Maharashtra, India.
authors.forename: Sudeep
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Cellular and Molecular Biology, The University of Texas Health Science Center at Tyler, Tyler, Texas. santanu.dasgupta@uthct.edu.
authors.forename: Santanu
authors.initials: S
authors.lastname: Dasgupta
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000175:diagnosis / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D045304:Cytochromes c / Q000378:metabolism; D018450:Disease Progression; D055354:Exosomes / Q000378:metabolism; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D061986:MCF-7 Cells; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D024101:Mitochondrial Proteins; C107640:SH3GL2 protein, human; D025521:Tumor Suppressor Proteins; D013481:Superoxides; D045304:Cytochromes c; D020558:GTP Phosphohydrolases; C470018:MFN2 protein, human