title: The epigenetic silencing of LIMS2 in gastric cancer and its inhibitory effect on cell migration.
abstract: Recent finding has shown that LIMS2 (also known as PINCH2) functions as a natural regulator of the LIMS1-ILK-parvin complex formation and is associated with cell spreading and migration via integrins at focal adhesions. Here, we report for the first time the epigenetic silencing of LIMS2 in gastric tumors. Downregulation of LIMS2 was detected in 91% (10 of 11) of gastric cancer cell lines by real-time quantitative RT-PCR and 80% (8 of 10) of the LIMS2-downregulated cell lines were associated with CpG island hypermethylation at a 5'-upstream region of LIMS2. Furthermore, LIMS2 was restored in its non-expressing cell lines after treatment with 5-Aza-dC and/or trichostatin A. Loss of expression of LIMS2 was also detected in 53% (51 of 96) of primary gastric tumors. This decrease in expression level significantly correlated with an increase of the CpG island hypermethylation. In addition, the methylation status in any normal-appearing gastric tissues was gradually increased in an age-dependent manner, suggesting that the positive methylation in normal-appearing gastric mucosa can be due to 'field cancerization effect' as an early event in gastric carcinogenesis. Moreover, the transient transfection of LIMS2-siRNA significantly stimulated cell migration in gastric cancer cells but had no effects on cell growth. These results suggest that the frequent inactivation of LIMS2 by epigenetic alteration in gastric cancer may be important in tumor progression events, such as invasion and metastasis. Thus, LIMS2 may be useful as a molecular biomarker and a therapeutic target by increasing its expression and activity in gastric cancer.
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 52 Eoeun-dong, Yuseong-gu, Daejeon 305-333, Republic of Korea.
authors.forename: Seung-Kyoon
authors.initials: SK
authors.lastname: Kim
authors.forename: Hae-Ran
authors.initials: HR
authors.lastname: Jang
authors.forename: Jeong-Hwan
authors.initials: JH
authors.lastname: Kim
authors.forename: Seung-Moo
authors.initials: SM
authors.lastname: Noh
authors.forename: Kyu-Sang
authors.initials: KS
authors.lastname: Song
authors.forename: Mi-Rang
authors.initials: MR
authors.lastname: Kim
authors.forename: Seun-Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Young-Il
authors.initials: YI
authors.lastname: Yeom
authors.forename: Nam-Soon
authors.initials: NS
authors.lastname: Kim
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Yoo
authors.forename: Yong Sung
authors.initials: YS
authors.lastname: Kim
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; C490235:LIMS2 protein, human; D008565:Membrane Proteins