Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway
Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most malignant digestive tumors, and its insidious onset and rapid progression are the main reasons for the difficulty in effective treatment. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a key enzyme that regulates p...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Annals of Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1665268122000229 |
| _version_ | 1811307238656049152 |
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| author | Ling Shen Peng Gu Chen Qiu Wen-tao Ding Lei Zhang Wan-yue Cao Zu-yin Li Bin Yan Xing Sun |
| author_facet | Ling Shen Peng Gu Chen Qiu Wen-tao Ding Lei Zhang Wan-yue Cao Zu-yin Li Bin Yan Xing Sun |
| author_sort | Ling Shen |
| collection | DOAJ |
| description | Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most malignant digestive tumors, and its insidious onset and rapid progression are the main reasons for the difficulty in effective treatment. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a key enzyme that regulates phospholipid metabolism of the cell membrane. However, the mechanism by which LPCAT1 regulates HCC metastasis remains unknown. This study aimed to explore its biological function and potential mechanisms concerning migration and invasion in HCC. Materials and methods: LPCAT1 expression in HCC tissues and its association with clinical outcomes were investigated by western blotting and bioinformatic methods, respectively. The role of LPCAT1 in migration and invasion was assessed via Transwell assays. The expression pattern of epithelial-mesenchymal transition (EMT) markers was quantified by western blotting. The biological behaviors of LPCAT1 in vivo were evaluated using xenograft tumor models and caudal vein metastatic models. Signaling pathways related to LPCAT1 were predicted using gene set enrichment analysis (GSEA) and further confirmed by western blotting. Results: LPCAT1 expression was significantly upregulated in HCC tissues and indicated a poor prognosis of HCC patients. Several EMT-related markers were found to be regulated by LPCAT1. HCC cells overexpressing LPCAT1 exhibited remarkably high migration and invasion capacities, upregulated expression of mesenchymal markers and reduced E-cadherin expression. In vivo, LPCAT1 promoted HCC pulmonary metastasis. Furthermore, the Wnt/β-catenin signaling pathway was confirmed to be activated by LPCAT1. Conclusions: LPCAT1 could serve as a promising biomarker of HCC and as a novel therapeutic target for the treatment of metastatic HCC. |
| first_indexed | 2024-04-13T09:00:43Z |
| format | Article |
| id | doaj.art-1d0c487260434413aafde4790c1ba4c5 |
| institution | Directory Open Access Journal |
| issn | 1665-2681 |
| language | English |
| last_indexed | 2024-04-13T09:00:43Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Annals of Hepatology |
| spelling | doaj.art-1d0c487260434413aafde4790c1ba4c52022-12-22T02:53:09ZengElsevierAnnals of Hepatology1665-26812022-05-01273100680Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathwayLing Shen0Peng Gu1Chen Qiu2Wen-tao Ding3Lei Zhang4Wan-yue Cao5Zu-yin Li6Bin Yan7Xing Sun8Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, China; Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaInstitute of Gallstone Disease, Center of Gallbladder Disease, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaIntervention Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Hepatobiliary Surgery, Peking University Organ Transplantation Institute, Peking University People's Hospital, Beijing, ChinaDepartment of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author at: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Clinical Medical School, Shanghai General Hospital of Nanjing Medical University, Shanghai, China; Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Corresponding author at: Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.Introduction and objectives: Hepatocellular carcinoma (HCC) is one of the most malignant digestive tumors, and its insidious onset and rapid progression are the main reasons for the difficulty in effective treatment. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is a key enzyme that regulates phospholipid metabolism of the cell membrane. However, the mechanism by which LPCAT1 regulates HCC metastasis remains unknown. This study aimed to explore its biological function and potential mechanisms concerning migration and invasion in HCC. Materials and methods: LPCAT1 expression in HCC tissues and its association with clinical outcomes were investigated by western blotting and bioinformatic methods, respectively. The role of LPCAT1 in migration and invasion was assessed via Transwell assays. The expression pattern of epithelial-mesenchymal transition (EMT) markers was quantified by western blotting. The biological behaviors of LPCAT1 in vivo were evaluated using xenograft tumor models and caudal vein metastatic models. Signaling pathways related to LPCAT1 were predicted using gene set enrichment analysis (GSEA) and further confirmed by western blotting. Results: LPCAT1 expression was significantly upregulated in HCC tissues and indicated a poor prognosis of HCC patients. Several EMT-related markers were found to be regulated by LPCAT1. HCC cells overexpressing LPCAT1 exhibited remarkably high migration and invasion capacities, upregulated expression of mesenchymal markers and reduced E-cadherin expression. In vivo, LPCAT1 promoted HCC pulmonary metastasis. Furthermore, the Wnt/β-catenin signaling pathway was confirmed to be activated by LPCAT1. Conclusions: LPCAT1 could serve as a promising biomarker of HCC and as a novel therapeutic target for the treatment of metastatic HCC.http://www.sciencedirect.com/science/article/pii/S1665268122000229LPCAT1Hepatocellular carcinomaMigration and invasionEMTWnt/β-catenin pathway |
| spellingShingle | Ling Shen Peng Gu Chen Qiu Wen-tao Ding Lei Zhang Wan-yue Cao Zu-yin Li Bin Yan Xing Sun Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway Annals of Hepatology LPCAT1 Hepatocellular carcinoma Migration and invasion EMT Wnt/β-catenin pathway |
| title | Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway |
| title_full | Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway |
| title_fullStr | Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway |
| title_full_unstemmed | Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway |
| title_short | Lysophosphatidylcholine acyltransferase 1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma via the Wnt/β-catenin signaling pathway |
| title_sort | lysophosphatidylcholine acyltransferase 1 promotes epithelial mesenchymal transition of hepatocellular carcinoma via the wnt β catenin signaling pathway |
| topic | LPCAT1 Hepatocellular carcinoma Migration and invasion EMT Wnt/β-catenin pathway |
| url | http://www.sciencedirect.com/science/article/pii/S1665268122000229 |
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