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Open AccessArticle

PI3K/AKT/β-Catenin Signaling Regulates Vestigial-Like 1 Which Predicts Poor Prognosis and Enhances Malignant Phenotype in Gastric Cancer

1
Personalized Genomic Medicine Research Center, KRIBB, Daejeon 34141, Korea
2
Department of Surgery, Yonsei University College of Medicine, Seoul 03722, Korea
3
Serverance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea
4
Biotherapeutics Translational Research Center, KRIBB, Daejeon 34141, Korea
5
Immunotherapy Convergence Research Center, KRIBB, Daejeon 34141, Korea
6
KRIBB School of Bioscience, Korea University of Science and Technology, Daejeon 34113, Korea
*
Authors to whom correspondence should be addressed.
These authors contribute equally to this work.
Cancers 2019, 11(12), 1923; https://doi.org/10.3390/cancers11121923
Received: 25 October 2019 / Revised: 26 November 2019 / Accepted: 29 November 2019 / Published: 3 December 2019
(This article belongs to the Special Issue Recent Advances in Gastric Cancer)
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. View Full-Text
Keywords: gastric cancer; MMP9; PI3K; VGLL1 gastric cancer; MMP9; PI3K; VGLL1
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Kim, B.-K.; Cheong, J.-H.; Im, J.-Y.; Ban, H.S.; Kim, S.-K.; Kang, M.-J.; Lee, J.; Kim, S.-Y.; Park, K.-C.; Paik, S.; Won, M. PI3K/AKT/β-Catenin Signaling Regulates Vestigial-Like 1 Which Predicts Poor Prognosis and Enhances Malignant Phenotype in Gastric Cancer. Cancers 2019, 11, 1923.

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