The novel protein suppressed in lung cancer down-regulated in lung cancer tissues retards cell proliferation and inhibits the oncokinase aurora-A

Chang Tze Ricky Yu, Jiun Yi Hsia, Yun Chih Hseih, Li Jen Su, Tien Chiang Lee, Chia Feng Ku, Ke Shin Chen, Jou May Maureen Chen, Tong You Wade Wei, Yuan Chii Gladys Lee, Chi Ying F Huang, Yu Chung Wu, Chiou Ying Yang, Shih Lan Hsu

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Introduction: 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.

Original languageEnglish
Pages (from-to)988-997
Number of pages10
JournalJournal of Thoracic Oncology
Volume6
Issue number6
DOIs
Publication statusPublished - Jun 2011

Keywords

  • Aurora-A
  • KIAA0256
  • Mitosis
  • SLAN
  • Tumor suppressor

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

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    Yu, C. T. R., Hsia, J. Y., Hseih, Y. C., Su, L. J., Lee, T. C., Ku, C. F., Chen, K. S., Maureen Chen, J. M., Wade Wei, T. Y., Lee, Y. C. G., Huang, C. Y. F., Wu, Y. C., Yang, C. Y., & Hsu, S. L. (2011). The novel protein suppressed in lung cancer down-regulated in lung cancer tissues retards cell proliferation and inhibits the oncokinase aurora-A. Journal of Thoracic Oncology, 6(6), 988-997. https://doi.org/10.1097/JTO.0b013e318212692e