title: Epstein-Barr virus latent membrane protein-2A alters mitochondrial dynamics promoting cellular migration mediated by Notch signaling pathway.
abstract: Recently, migration and invasion of breast cancer cells have been linked with dysregulated mitochondrial dynamics. Mitochondria are essential cellular organelles that undergo continuous dynamic cycles of fission and fusion. It has been proposed that a delicate balance between these two processes is important for many pathophysiological outcomes including cancer. Epstein-Barr virus (EBV) is a gamma herpesvirus that is associated with various lymphoid and epithelial malignancies. The viral latent membrane protein 2A (LMP2A) has been shown to increase the invasive ability and induce epithelial-mesenchymal transition in nasopharyngeal carcinoma. Our present study reveals that mitochondrial dynamics also plays a critical role in Epstein-Barr virus-associated epithelial cancers. Our data indicate that viral LMP2A causes an elevated mitochondrial fission in gastric and breast cancer cells, which is manifested by elevated fission protein dynamin-related protein 1 (Drp1). Furthermore, LMP2A-mediated Notch pathway is responsible for this enhanced fission since inhibitors of the pathway decrease the expression of Drp1.
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Anindita Deb
authors.initials: AD
authors.lastname: Pal
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Nandini Pal
authors.initials: NP
authors.lastname: Basak
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India.
authors.forename: Aditi Sengupta
authors.initials: AS
authors.lastname: Banerjee
authors.affiliation: Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064, India subrata.banerjee@saha.ac.in.
authors.forename: Subrata
authors.initials: S
authors.lastname: Banerjee
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D034281:Dynamins; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005434:Flow Cytometry; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D063154:Mitochondrial Dynamics; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D014763:Viral Matrix Proteins; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins