FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR
Abstract Background Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been linked to tumor progression in many types of cancer. The role of FGFR3 in melanoma remains unclear. In this study, we aimed to uncover the role of FGFR3 in the growth and metastasis of melanoma. Methods FGFR3...
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doaj-36480d40c3d24b839176a2070d096a952020-11-25T03:53:05ZengBMCBMC Cancer1471-24072019-10-0119111210.1186/s12885-019-6161-8FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFRLei Li0Shuai Zhang1Hao Li2Haiyan Chou3Department of Plastic and Cosmetic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Plastic and Cosmetic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou UniversityDepartment of Plastic and Cosmetic Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou UniversityAbstract Background Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been linked to tumor progression in many types of cancer. The role of FGFR3 in melanoma remains unclear. In this study, we aimed to uncover the role of FGFR3 in the growth and metastasis of melanoma. Methods FGFR3 knockdown and overexpression strategies were employed to investigate the effects of FGFR3 on colony formation, cell apoptosis, proliferation, migration, and in vitro invasion, along with the growth and metastasis of melanoma in a xenografts mouse model. The protein expression levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), epidermal growth factor receptor (EGFR), and epithelial-mesenchymal transition (EMT) markers were determined by Western blot analysis. Results The mRNA expression of FGFR3 was higher in melanoma tissues than normal healthy tissues. FGFR3 expression in cutaneous malignant melanoma (CMM) tissues was positively correlated with the Breslow thickness and lymph node metastasis. In A357 cells, knockdown of the FGFR3 gene decreased the colony formation ability, cell proliferation, invasion, and migration, but increased the caspase 3 activity and the apoptosis rate; overexpression of FGFR3 increased the colony formation ability, cell proliferation, invasion, and migration, but decreased the caspase 3 activity and apoptosis rates. FGFR3 knockdown also upregulated E-cadherin, downregulated N-cadherin and vimentin, and decreased the phosphorylation levels of ERK, AKT, and EGFR. In the MCC xenografts mice, knockdown of FGFR3 decreased tumor growth and metastasis. Conclusions FGFR3, which is highly expressed in CMM tissues, is correlated with increased Breslow thickness and lymph node metastasis. FGFR3 promotes melanoma growth, metastasis, and EMT behaviors, likely by affecting the phosphorylation levels of ERK, AKT, and EGFR.http://link.springer.com/article/10.1186/s12885-019-6161-8FGFR3MelanomaMetastasisEpithelial-mesenchymal transitionERKAKT |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lei Li Shuai Zhang Hao Li Haiyan Chou |
spellingShingle |
Lei Li Shuai Zhang Hao Li Haiyan Chou FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR BMC Cancer FGFR3 Melanoma Metastasis Epithelial-mesenchymal transition ERK AKT |
author_facet |
Lei Li Shuai Zhang Hao Li Haiyan Chou |
author_sort |
Lei Li |
title |
FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR |
title_short |
FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR |
title_full |
FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR |
title_fullStr |
FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR |
title_full_unstemmed |
FGFR3 promotes the growth and malignancy of melanoma by influencing EMT and the phosphorylation of ERK, AKT, and EGFR |
title_sort |
fgfr3 promotes the growth and malignancy of melanoma by influencing emt and the phosphorylation of erk, akt, and egfr |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2019-10-01 |
description |
Abstract Background Overexpression of fibroblast growth factor receptor 3 (FGFR3) has been linked to tumor progression in many types of cancer. The role of FGFR3 in melanoma remains unclear. In this study, we aimed to uncover the role of FGFR3 in the growth and metastasis of melanoma. Methods FGFR3 knockdown and overexpression strategies were employed to investigate the effects of FGFR3 on colony formation, cell apoptosis, proliferation, migration, and in vitro invasion, along with the growth and metastasis of melanoma in a xenografts mouse model. The protein expression levels of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), epidermal growth factor receptor (EGFR), and epithelial-mesenchymal transition (EMT) markers were determined by Western blot analysis. Results The mRNA expression of FGFR3 was higher in melanoma tissues than normal healthy tissues. FGFR3 expression in cutaneous malignant melanoma (CMM) tissues was positively correlated with the Breslow thickness and lymph node metastasis. In A357 cells, knockdown of the FGFR3 gene decreased the colony formation ability, cell proliferation, invasion, and migration, but increased the caspase 3 activity and the apoptosis rate; overexpression of FGFR3 increased the colony formation ability, cell proliferation, invasion, and migration, but decreased the caspase 3 activity and apoptosis rates. FGFR3 knockdown also upregulated E-cadherin, downregulated N-cadherin and vimentin, and decreased the phosphorylation levels of ERK, AKT, and EGFR. In the MCC xenografts mice, knockdown of FGFR3 decreased tumor growth and metastasis. Conclusions FGFR3, which is highly expressed in CMM tissues, is correlated with increased Breslow thickness and lymph node metastasis. FGFR3 promotes melanoma growth, metastasis, and EMT behaviors, likely by affecting the phosphorylation levels of ERK, AKT, and EGFR. |
topic |
FGFR3 Melanoma Metastasis Epithelial-mesenchymal transition ERK AKT |
url |
http://link.springer.com/article/10.1186/s12885-019-6161-8 |
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