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KMID : 0578320230460050298
Molecules and Cells
2023 Volume.46 No. 5 p.298 ~ p.308
Epigenetic Activation of Tensin 4 Promotes Gastric Cancer Progression
Heo Hae-Jeong

Kim Hee-Jin
Haam Kee-Ok
Sohn Hyun-Ahm
Shin Yang-Ji
Yikai Qiu
Xiaoli Yu
Kim Jong-Hwan
Lee Sang-Il
Song Kyu-Sang
Kim Min-Ju
Lee Hae-Seung
Kwon Eun-Soo
Kim Seon-Young
Ogbeide Philip Aihebholoria
Kim Mi-Rang
Abstract
Gastric cancer (GC) is a complex disease influenced by multiple genetic and epigenetic factors. Chronic inflammation caused by Helicobacter pylori infection and dietary risk factors can result in the accumulation of aberrant DNA methylation in gastric mucosa, which promotes GC development. Tensin 4 (TNS4), a member of the Tensin family of proteins, is localized to focal adhesion sites, which connect the extracellular matrix and cytoskeletal network. We identified upregulation of TNS4 in GC using quantitative reverse transcription PCR with 174 paired samples of GC tumors and adjacent normal tissues. Transcriptional activation of TNS4 occurred even during the early stage of tumor development. TNS4 depletion in GC cell lines that expressed high to moderate levels of TNS4, i.e., SNU-601, KATO III, and MKN74, reduced cell proliferation and migration, whereas ectopic expression of TNS4 in those lines that expressed lower levels of TNS4, i.e., SNU-638, MKN1, and MKN45 increased colony formation and cell migration. The promoter region of TNS4 was hypomethylated in GC cell lines that showed upregulation of TNS4. We also found a significant negative correlation between TNS4 expression and CpG methylation in 250 GC tumors based on The Cancer Genome Atlas (TCGA) data. This study elucidates the epigenetic mechanism of TNS4 activation and functional roles of TNS4 in GC development and progression and suggests a possible approach for future GC treatments.
KEYWORD
cell migration, cell proliferation, DNA methylation, gastric cancer, TNS4
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