Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway
Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vi...
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doaj-4783aaf35641407083cdc570289395312020-12-21T11:41:29ZengHindawi LimitedJournal of Immunology Research2314-88612314-71562020-01-01202010.1155/2020/67654746765474Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP PathwayJia-Huang Liu0Qi-Fei Wu1Jun-Ke Fu2Xiang-Ming Che3Hai-Jun Li4Department of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of General Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaDepartment of Thoracic Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaObesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly (P<0.05); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly (P<0.05) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly (P<0.05); YAP and MMP9 mRNA expression increased significantly (P<0.05) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect.http://dx.doi.org/10.1155/2020/6765474 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jia-Huang Liu Qi-Fei Wu Jun-Ke Fu Xiang-Ming Che Hai-Jun Li |
spellingShingle |
Jia-Huang Liu Qi-Fei Wu Jun-Ke Fu Xiang-Ming Che Hai-Jun Li Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway Journal of Immunology Research |
author_facet |
Jia-Huang Liu Qi-Fei Wu Jun-Ke Fu Xiang-Ming Che Hai-Jun Li |
author_sort |
Jia-Huang Liu |
title |
Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway |
title_short |
Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway |
title_full |
Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway |
title_fullStr |
Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway |
title_full_unstemmed |
Obesity Potentiates Esophageal Squamous Cell Carcinoma Growth and Invasion by AMPK-YAP Pathway |
title_sort |
obesity potentiates esophageal squamous cell carcinoma growth and invasion by ampk-yap pathway |
publisher |
Hindawi Limited |
series |
Journal of Immunology Research |
issn |
2314-8861 2314-7156 |
publishDate |
2020-01-01 |
description |
Obesity could increase the risk of esophageal squamous cell carcinoma (ESCC) and affect its growth and progression, but the mechanical links are unclear. The objective of the study was to explore the impact of obesity on ESCC growth and progression utilizing in vivo trials and cell experiments in vitro. Diet-induced obese and lean nude mice were inoculated with TE-1 cells, then studied for 4 weeks. Serum glucose, insulin, leptin, and visfatin levels were assayed. Sera of nude mice were obtained and then utilized to culture TE-1. MTT, migration and invasion assays, RT-PCR, and Western blotting were used to analyze endocrine effect of obesity on cell proliferation, migration, invasion, and related genes expression of TE-1. Obese nude mice bore larger tumor xenografts than lean animals, and were hyperglycemic and hyperinsulinemic with an elevated level of leptin and visfatin in sera, and also were accompanied by a fatty liver. As for the subcutaneous tumor xenograft model, tumors were more aggressive in obese nude mice than lean animals. Tumor weight correlated positively with mouse body weight, liver weight of mice, serum glucose, HOMA-IR, leptin, and visfatin. Obesity prompted significant TE-1 cell proliferation, migration, and invasion by endocrine mechanisms and impacted target genes. The expression of AMPK and p-AMPK protein decreased significantly (P<0.05); MMP9, total YAP, p-YAP, and nonphosphorylated YAP protein increased significantly (P<0.05) in the cells cultured with conditioned media and xenograft tumor from the obese group; the mRNA expression of AMPK decreased significantly (P<0.05); YAP and MMP9 mRNA expression increased significantly (P<0.05) in the cells exposed to conditioned media from the obese group. In conclusion, the altered adipokine milieu and metabolites in the context of obesity may promote ESCC growth in vivo; affect proliferation, migration, and invasion of ESCC cells in vitro; and regulate MMP9 and AMPK-YAP signaling pathway through complex effects including the endocrine effect. |
url |
http://dx.doi.org/10.1155/2020/6765474 |
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