Mei Liu1, Yuan-Bin Zhong2, Jia Shao3, Cheng Zhang4, Chao Shi1. 1. Department of Oncology, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi Province, P. R China. 2. Department of Infectious Diseases & Key Laboratory of Liver Regenerative Medicine of Jiangxi Province, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi Province, P. R China. 3. Department of Assisted Reproductive, The First Affiliated Hospital of Nanchang University , Nanchang, Jiangxi Province, P. R China. 4. School of Basic Medical Sciences, Nanchang University , Nanchang, Jiangxi Province, P. R China.
Abstract
AIM: In this study, we explored the ability of TAMs to affect the malignant phenotype of human hepatoma Huh-7 cells through the Gli2/IGF-II/ERK1/2 pathway. METHODS: The TAMs were characterized by flow cytometry and ELISA assays. Huh-7 cells were treated with conditioned medium of TAMs (TAMs-CM), and the proliferation, migration and invasion abilities were measured by CCK-8, Transwell and scratch assays. The levels of TGF-β1, Gli2, IGF-II and related proteins in the ERK1/2 pathway and the epithelial-mesenchymal transition (EMT) process were examined by RT-qPCR and western blot. Huh-7 cells were injected subcutaneously into nude mice with TAMs to explore the role of TAMs in tumor growth. RESULTS: The expression levels of TGF-β1, Gli2 and IGF-II and the cell proliferation, migration and invasion abilities were elevated in Huh-7 cells treated with TAMs-CM. TGF-β1 was upregulated in the conditioned medium and was found to be involved in the promotion of migration, invasion and the EMT of Huh-7 cells. The activation of TGF-β1 signaling increased the expression of Gli2. Knockdown of Gli2 decreased the expression of IGF-II and also reversed the promotional effect of the conditioned medium on migration, invasion and the EMT of Huh-7 cells. TGF-β1/Gli2/IGF-II signaling was shown to promote the malignant phenotype of Huh-7 cells by activating the ERK1/2 signaling pathway. Further, TGF-β1 knockdown attenuated the influence of TAMs on tumor growth in mouse model. CONCLUSION: The TGF-β1 secreted by TAMs promotes the migration, invasion and EMT of human hepatoma Huh-7 cells through the Gli2/IGF-II/ERK1/2 pathway.
AIM: In this study, we explored the ability of TAMs to affect the malignant phenotype of humanhepatomaHuh-7 cells through the Gli2/IGF-II/ERK1/2 pathway. METHODS: The TAMs were characterized by flow cytometry and ELISA assays. Huh-7 cells were treated with conditioned medium of TAMs (TAMs-CM), and the proliferation, migration and invasion abilities were measured by CCK-8, Transwell and scratch assays. The levels of TGF-β1, Gli2, IGF-II and related proteins in the ERK1/2 pathway and the epithelial-mesenchymal transition (EMT) process were examined by RT-qPCR and western blot. Huh-7 cells were injected subcutaneously into nude mice with TAMs to explore the role of TAMs in tumor growth. RESULTS: The expression levels of TGF-β1, Gli2 and IGF-II and the cell proliferation, migration and invasion abilities were elevated in Huh-7 cells treated with TAMs-CM. TGF-β1 was upregulated in the conditioned medium and was found to be involved in the promotion of migration, invasion and the EMT of Huh-7 cells. The activation of TGF-β1 signaling increased the expression of Gli2. Knockdown of Gli2 decreased the expression of IGF-II and also reversed the promotional effect of the conditioned medium on migration, invasion and the EMT of Huh-7 cells. TGF-β1/Gli2/IGF-II signaling was shown to promote the malignant phenotype of Huh-7 cells by activating the ERK1/2 signaling pathway. Further, TGF-β1 knockdown attenuated the influence of TAMs on tumor growth in mouse model. CONCLUSION: The TGF-β1 secreted by TAMs promotes the migration, invasion and EMT of humanhepatomaHuh-7 cells through the Gli2/IGF-II/ERK1/2 pathway.
Authors: S S Islam; R B Mokhtari; A S Noman; M Uddin; M Z Rahman; M A Azadi; A Zlotta; T van der Kwast; H Yeger; W A Farhat Journal: Mol Carcinog Date: 2015-03-01 Impact factor: 4.784
Authors: Saravanan Thiyagarajan; Neehar Bhatia; Shannon Reagan-Shaw; Diana Cozma; Andrei Thomas-Tikhonenko; Nihal Ahmad; Vladimir S Spiegelman Journal: Cancer Res Date: 2007-11-15 Impact factor: 12.701
Authors: Sylviane Dennler; Jocelyne André; Ismini Alexaki; Allen Li; Thierry Magnaldo; Peter ten Dijke; Xiao-Jing Wang; Franck Verrecchia; Alain Mauviel Journal: Cancer Res Date: 2007-07-15 Impact factor: 12.701
Authors: Armel H Nwabo Kamdje; Paul F Seke Etet; Maulilio J Kipanyula; Lorella Vecchio; Richard Tagne Simo; Alfred K Njamnshi; Kiven E Lukong; Patrice N Mimche Journal: Front Endocrinol (Lausanne) Date: 2022-08-09 Impact factor: 6.055