title: Aurora-A, a negative prognostic marker, increases migration and decreases radiosensitivity in cancer cells.
abstract: Centrosomal Aurora-A (Aur-A) kinase ensures proper spindle assembly and accurate chromosome segregation in mitosis. Overexpression of Aur-A leads to centrosome amplification, aberrant spindle, and consequent genetic instability. In the present study, Aur-A was found to be overexpressed in laryngeal squamous cell carcinoma (LSCC). Moreover, Aur-A expression was adversely correlated with median survival, and further identified as a potential independent factor for disease prognosis. Suppression of Aurora kinase activity chemically or genetically led to LSCC Hep2 cell cycle arrest and apoptotic cell death. Importantly, we found that Aur-A increases cell migration and this novel function was correlated with Akt1 activation. The enhanced cell migration induced by Aur-A overexpression could be abrogated by either small-molecule Akt1 inhibitor or short interfering RNA. VX-680, a selective Aurora kinase inhibitor, decreased Akt1 phosphorylation at Ser(473) and inhibited cell migration, but failed to do so in constitutive active Akt1 (myr-Akt1)-overexpressed cells. Moreover, our data suggested that overexpression of Aur-A kinase might also contribute to radioresistance of LSCC. Inhibiting Aur-A by VX-680 induced expression of p53 and potently sensitized cells to radiotherapy, leading to significant cell death. Ectopic overexpression of Aur-A, however, reduced p53 level and rendered cells more resistant to irradiation. Taken together, we showed that Aur-A kinase, a negative prognostic marker, promotes migration and reduces radiosensitivity in laryngeal cancer cells.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Guan
authors.forename: Xian-ren
authors.initials: XR
authors.lastname: Wang
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Zhu
authors.forename: Xue-fei
authors.initials: XF
authors.lastname: Huang
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Li-hui
authors.initials: LH
authors.lastname: Wang
authors.forename: Xiang-bo
authors.initials: XB
authors.lastname: Wan
authors.forename: Zi-jie
authors.initials: ZJ
authors.lastname: Long
authors.forename: Jian-nan
authors.initials: JN
authors.lastname: Liu
authors.forename: Gong-kan
authors.initials: GK
authors.lastname: Feng
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.forename: Yi-xin
authors.initials: YX
authors.lastname: Zeng
authors.forename: Fu-jin
authors.initials: FJ
authors.lastname: Chen
authors.forename: Quentin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D064127:Aurora Kinases; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D006801:Humans; D007822:Laryngeal Neoplasms / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy; D010879:Piperazines / Q000494:pharmacology; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D034741:RNA, Small Interfering / Q000494:pharmacology; D011836:Radiation Tolerance; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines
chemical_list: D064127:Aurora Kinases; D010879:Piperazines; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C484810:tozasertib; D003521:Cyclopropanes; D011720:Pyrazoles; D011743:Pyrimidines; C494918:AKT1 protein, human