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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Main Authors: Lei Li, Shuai Zhang, Hao Li, Haiyan Chou
Format: Article
Language:English
Published: BMC 2019-10-01
Series:BMC Cancer
Subjects:
ERK
AKT
Online Access:http://link.springer.com/article/10.1186/s12885-019-6161-8
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spelling 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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