title: Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation.
abstract: Revival of dormant tumor cells may be an important tumor metastasis mechanism. We hypothesized that aurora kinase A (AURKA), a cell cycle control kinase, promotes the transition of laryngeal squamous cell carcinoma (LSCC) cells from G0 phase to active division. We therefore investigated whether AURKA could revive dormant tumor cells to promote metastasis. Western blotting revealed that AURKA expression was persistently low in dormant laryngeal cancer Hep2 (D-Hep2) cells and high in non-dormant (T-Hep2) cells. Decreasing AURKA expression in T-Hep2 cells induced dormancy and reduced FAK/PI3K/Akt pathway activity. Increasing AURKA expression in D-Hep2 cells increased FAK/PI3K/Akt pathway activity and enhanced cellular proliferation, migration, invasion and metastasis. In addition, FAK/PI3K/Akt pathway inhibition caused dormancy-like behavior and reduced cellular mobility, migration and invasion. We conclude that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment.
authors.affiliation: Department of Otolaryngology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chang-Yu
authors.initials: CY
authors.lastname: He
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Xue-Hua
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Su
authors.affiliation: Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Bing-Ya
authors.initials: BY
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation / Q000502:physiology; D015536:Down-Regulation; D051417:Focal Adhesion Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D064593:Heterografts; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D014162:Transfection
chemical_list: D064096:Aurora Kinase A; D051417:Focal Adhesion Kinase 1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; C496050:PTK2 protein, human; C576917:AURKA protein, human
keywords: Akt; FAK; PI3K; aurora kinase A; laryngeal cancer