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KMID : 0939920130450020134
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대한암학회지
2013 Volume.45 No. 2 p.134 ~ p.144
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RASSF1A Suppresses Cell Migration through Inactivation of HDAC6 and Increase of Acetylated α-Tubulin
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Jung Hae-Yun
Jung Jun-Seok
Whang Young-Mi
Kim Yeul-Hong
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Abstract
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Purpose: The RAS association domain family protein 1 (RASSF1) has been implicated in a tumor-suppressive function through the induction of acetylated α-tubulin and modulation of cell migration. However, the mechanisms of how RASSF1A is associated with acetylation of α-tubulin for controlling cell migration have not yet been elucidated. In this study, we found that RASSF1A regulated cell migration through the regulation of histon deacetylase 6 (HDAC6), which functions as a tubulin deacetylase.
Materials and Methods: The cell migration was assessed using wound-healing and transwell assays. The role of RASSF1A on cell migration was examined by immunofluorescence staining, HDAC activity assay and western blot analysis.
Results: Cell migration was inhibited and cell morphology was changed in RASSF1A-transfected H1299 cells, compared with controls, whereas HDAC6 protein expression was not changed by RASSF1A transfection in these cells. However, RASSF1A inhibited deacetylating activity of HDAC6 protein and induced acetylated α-tubulin expression. Furthermore, acetylated α-tubulin and HDAC6 protein were co-localized in the cytoplasm in RASSF1A-transfected H1299 cells. Conversely, when the endogenous RASSF1A expression in HeLa cells was blocked with RASSF1A siRNA treatment, acetylated α-tubulin was co-localized with HDAC6 protein throughout the whole cells, including the nucleus, compared with scramble siRNA-treated HeLa cells. The restoration of RASSF1A by 5-Aza-dC treatment also induced acetylated α-tubulin through inhibition of HDAC6 activity that finally resulted in suppressing cell migration in H1299 cells. To further confirm the role of HDAC6 in RASSF1A-mediated cell migration, the HDAC6 expression in H1299 cells was suppressed by using HDAC6 siRNA, and cell motility was found to be decreased through enhanced acetylated α-tubulin.
Conclusion: The results of this study suggest that the inactivation of HDAC6 by RASSF1A regulates cell migration through increased acetylated α-tubulin protein.
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KEYWORD
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Cell movement, HDAC6, Lung neoplasms, RASSF1A, Tumor suppressor genes
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