PI3K/AKT/β-catenin signaling regulates vestigial-like 1 which predicts poor prognosis and enhances malignant phenotype in gastric cancer = PI3K/AKT/β-catenin 신호전달이 위암 악성화에 관여하는 VGLL1 조절에 기여
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- PI3K/AKT/β-catenin signaling regulates vestigial-like 1 which predicts poor prognosis and enhances malignant phenotype in gastric cancer = PI3K/AKT/β-catenin 신호전달이 위암 악성화에 관여하는 VGLL1 조절에 기여
- Bo Kyung Kim; J H Cheong; Joo-Young Im; Hyun Seung Ban; Seon-Kyu Kim; Mi-Jung Kang; Jungwoon Lee; Seon-Young Kim; Kyung Chan Park; S Paik; Mi Sun Won
- Bibliographic Citation
- Cancers, vol. 11, pp. 1923-1923
- Publication Year
- Although gastric cancer is a common cause of cancer mortality worldwide, its biological heterogeneity limits the available therapeutic options. Therefore, identifying novel therapeutic targets for developing effective targeted therapy of gastric cancer is a pressing need. Here, we investigate molecular function and regulatory mechanisms of Vestigial-like 1 (VGLL1) in gastric cancer. Microarray analysis of 556 gastric cancer tissues revealed that VGLL1 was a prognostic biomarker that correlated with PI3KCA and PI3KCB. VGLL1 regulates the proliferation of gastric cancer cells, as shown in live cell imaging, sphere formation, and in vivo xenograft model. Tail vein injection of NUGC3 cells expressing shVGLL1 resulted in less lung metastasis occurring when compared to the control. In contrast, larger metastatic lesions in lung and liver were detected in the VGLL1-overexpressing NUGC3 cell xenograft excision mouse model. Importantly, VGLL1 expression is transcriptionally regulated by the PI3K-AKT-β-catenin pathway. Subsequently, MMP9, a key molecule in gastric cancer, was explored as one of target genes that were transcribed by VGLL1-TEAD4 complex, a component of the transcription factor. Taken together, PI3K/AKT/β-catenin signaling regulates the transcription of VGLL1, which promotes the proliferation and metastasis in gastric cancer. This finding suggests VGLL1 as a novel prognostic biomarker and a potential therapeutic target.
- MMP9; PI3K; VGLL1; gastric cancer
- Appears in Collections:
- Division of Biomedical Research > Personalized Genomic Medicine Research Center > 1. Journal Articles
Division of Biomedical Research > Biotherapeutics Translational Research Center > 1. Journal Articles
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Korea Bioinformation Center > 1. Journal Articles
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