title: Mitochondrial dynamics regulating chemoresistance in gynecological cancers.
abstract: Chemoresistance enables cancer cells to evade apoptotic stimuli and leads to poor clinical prognosis. It arises from dysregulation of signaling factors responsible for inducing cell proliferation and death and for modulating the microenvironment. In gynecologic cancers, p53 is a pivotal determinant of cisplatin sensitivity, while BCL-2 family members are associated with taxane sensitivity. Mitochondria fusion and fission dynamics are required for many mitochondrial functions and are also involved in mitochondria-mediated apoptosis, which is closely associated with chemosensitivity. Mitochondrial dynamics are controlled by a number of intracellular proteins, including fusion (Opa1 and mitofusion 1 and 2) and fission proteins (Drp1 and Fis1), which can be proapoptotic or antiapoptotic, depending on the cell types, status, and stimuli from the microenvironment. This paper describes the role of mitochondrial dynamics in the mechanism of chemoresistance and the evidence supporting a significant contribution of a hyperfusion state to chemoresistance in gynecological cancers. Moreover, we discuss our findings showing that enforced fission induces apoptosis of cancer cells and sensitizes them to chemotherapeutic agents. Understanding the regulation of mitochondrial dynamics in chemoresistance may provide insight into new biomarkers that better predict cancer chemosensitivity and may aid the development of effective therapeutic strategies for clinical management of gynecologic cancers.
authors.affiliation: Department of Obstetrics and Gynecology, Department of Cellular and Molecular Medicine, and Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.|Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Bao
authors.initials: B
authors.lastname: Kong
authors.affiliation: Department of Obstetrics and Gynecology, Department of Cellular and Molecular Medicine, and Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.|Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Obstetrics and Gynecology, University of Fukui, Fukui, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Tsuyoshi
authors.affiliation: Department of Obstetrics and Gynecology, University of Fukui, Fukui, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Orisaka
authors.affiliation: Institute of Basic Medical Science, Institute of Oral Medicine, and Department of Stomatology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Dar-Bin
authors.initials: DB
authors.lastname: Shieh
authors.affiliation: Department of Obstetrics and Gynecology, University of Fukui, Fukui, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Obstetrics and Gynecology, Department of Cellular and Molecular Medicine, and Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.|Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Tsang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005836:Genitalia, Female / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D063154:Mitochondrial Dynamics / Q000187:drug effects*; D008954:Models, Biological
chemical_list: D000970:Antineoplastic Agents
keywords: CDDP; cancer; chemoresistance; mitochondrial dynamics