Metastasis-induction and apoptosis-protection by TWIST in gastric cancer cells.
TWIST, a basic helix-loop-helix transcription factor, has been recently reported to play an important role in tumorigenesis of human cancer through converting the early stage tumors into invasive malignancies. Upregulation of TWIST is often found in cancer patients, especially those with shorter survival period and poor response to chemotherapy. Here we studied the functions of TWIST on regulating migration rate, apoptosis, and gene expression in gastric cancer cells. TWIST expression is elevated in MGC-803 and HGC-27 cells that exhibit high invasive potential; whereas it is reduced in BGC-823 and SGC-7901 cells that possess relatively low invasive content. To evaluate functional consequences of TWIST induction, we examined the effect of TWIST on cell migration and apoptosis. Overexpression of TWIST in BGC-823 cells resulted in increased migration content and decreased sensitivity to the arsenic oxide-induced cell death. Moreover, small interference RNA-mediated TWIST ablation in MGC-803 and HGC-27 cells showed suppressed migration ability, increased induction of apoptosis in response to arsenic oxide, and elevated cell cycle arrest. Furthermore, we found a negative correlation between the TWIST level and p53 level, probably due to transcriptional regulation. Our results have identified TWIST as a critical regulator of gastric cancer cell proliferation and migration, suggesting a potential therapeutic approach to inhibit the growth and metastasis of gastric cancer through inactivation of TWIST.
Feng
Mei-yan
MY
The Pathology Department, Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
Wang
Kuan
K
Song
Hong-tao
HT
Yu
Hong-wei
HW
Qin
Yu
Y
Shi
Qing-tao
QT
Geng
Jing-shu
JS
D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000502:physiology*
D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D016159:Tumor Suppressor Protein p53; D051879:Twist-Related Protein 1