title: The novel protein suppressed in lung cancer down-regulated in lung cancer tissues retards cell proliferation and inhibits the oncokinase Aurora-A.
abstract: BACKGROUND
  In an attempt to search for genes with abnormal expression in cancers, Suppressed in Lung Cancer (SLAN, also known as KIAA0256) is found underexpressed in human lung cancer tissues by quantitative real-time PCR (Q-RT-PCR). The study set out to characterize SLAN protein and explore its cellular functions.
  
  
  METHODS
  SLAN or its specific short hairpin RNA, full length or various deletion mutants were overexpressed in 293T or lung cancer cell lines, and cell proliferation, cell cycle, mitosis progression, and spindle configuration were surveyed.
  
  
  RESULTS
  SLAN and its deletion mutants are localized to many subcellular locations such as endoplasmic reticulum (ER), nucleus, nucleolus, spindle pole and midbody, suggesting SLAN may function as a multifunctional protein. Overexpression of SLAN per se or its short hairpin RNAs (shRNAs) inhibits or accelerates cell proliferation through prolonging or shortening mitosis. Time-lapse microscopic recording reveals that cells overexpressing exogenous SLAN are arrested in mitosis or cannot undergo cytokinesis. SLAN 2-551 mutants drastically arrest cells in mitosis, where α- and γ-tubulin are disorganized. SLAN employs C-terminal to interact with Aurora-A, a key mitosis regulator and an oncogenic kinase associated with a wide range of human cancers. SLAN negatively regulates the activity of Aurora-A by directly inhibiting kinase activity in vitro or reducing the level of active Aurora-A in cells. SLAN is frequently reduced in lung cancer tissues overexpressing Aurora-A, arguing for the necessity to suppress SLAN during the Aurora-A-associated cancer formation.
  
  
  CONCLUSIONS
  Taken together, we have identified a novel protein SLAN downregulated in lung caner, having multiple subcellular localization including spindle matrix and midbody, inhibiting cell proliferation and Aurora-A.
authors.affiliation: Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Nantou, Taiwan.
authors.forename: Chang-Tze Ricky
authors.initials: CT
authors.lastname: Yu
authors.forename: Jiun-Yi
authors.initials: JY
authors.lastname: Hsia
authors.forename: Yun-Chih
authors.initials: YC
authors.lastname: Hseih
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Su
authors.forename: Tien-Chiang
authors.initials: TC
authors.lastname: Lee
authors.forename: Chia-Feng
authors.initials: CF
authors.lastname: Ku
authors.forename: Ke-Shin
authors.initials: KS
authors.lastname: Chen
authors.forename: Jou-May Maureen
authors.initials: JM
authors.lastname: Chen
authors.forename: Tong-You Wade
authors.initials: TY
authors.lastname: Wei
authors.forename: Yuan-Chii Gladys
authors.initials: YC
authors.lastname: Lee
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
authors.forename: Yu-Chung
authors.initials: YC
authors.lastname: Wu
authors.forename: Chiou-Ying
authors.initials: CY
authors.lastname: Yang
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
mesh_terms: D064127:Aurora Kinases; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D017384:Sequence Deletion; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; C562039:SECISBP2L protein, human; D025521:Tumor Suppressor Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases