title: Aurora kinase A has a significant role as a therapeutic target and clinical biomarker in endometrial cancer.
abstract: Aurora kinase A (AURKA) regulates the cell cycle checkpoint and maintains genomic integrity. AURKA is overexpressed in various malignant tumors and its upregulation induces chromosomal instability, which leads to aneuploidy and cell transformation. To investigate the role of AURKA in endometrial cancer, we evaluated the association of immunohistochemical expression of AURKA with clinicopathological factors. Furthermore, we examined the effects of AURKA inhibition by transfected siRNA in HEC-1B cells on colony-forming ability, invasion and migration capacity, and chemosensitivity. Immunohistochemical staining showed that overexpression of AURKA was significantly associated with tumor grade (P<0.05) and poor histologic differentiation (P<0.05). The recurrence rate also tended to be high in cases with overexpression of AURKA (P<0.1) and these cases also had a tendency for shorter disease-free survival (DFS) (P<0.1). AURKA inhibition in endometrial cancer cell lines significantly decreased cell growth, invasion and migration (P<0.05), and increased chemosensitivity to paclitaxel. We also evaluated the efficacy of a combination of AURKA siRNA and paclitaxel against subcutaneous tumors formed in a nude mouse. After treatment, the tumor volume shrank significantly compared to treatment with paclitaxel only (P<0.05). To our knowledge, this is the first study in endometrial carcinoma to show a correlation between overexpression of AURKA and tumor grade, histological type and sensitivity to paclitaxel. AURKA is a promising therapeutic target in endometrial cancer and the combination therapy with AURKA inhibitors and paclitaxel could be effective for endometrial cancer that is resistant to conventional treatment and has a poor prognosis.
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Umene
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Yanokura
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kouji
authors.initials: K
authors.lastname: Banno
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Irie
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Adachi
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Iida
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nogami
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Masuda
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Tominaga
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D064096:Aurora Kinase A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; C576917:AURKA protein, human; D064096:Aurora Kinase A; D017239:Paclitaxel