Silencing of LAMC2 Reverses Epithelial-Mesenchymal Transition and Inhibits Angiogenesis in Cholangiocarcinoma via Inactivation of the Epidermal Growth Factor Receptor Signaling Pathway

Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates...

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Veröffentlicht in:The American journal of pathology Jg. 189; H. 8; S. 1637
Hauptverfasser: Pei, Yao-Fei, Liu, Jie, Cheng, Jian, Wu, Wei-Ding, Liu, Xi-Qiang
Format: Journal Article
Sprache:Englisch
Veröffentlicht: United States 01.08.2019
Schlagworte:
Adult
Aged
Animals
Bile Duct Neoplasms - blood supply
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Cell Line, Tumor
Cholangiocarcinoma - blood supply
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
Epithelial-Mesenchymal Transition
ErbB Receptors - metabolism
Female
Gene Silencing
Humans
Laminin - metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Signal Transduction
Tumor Suppressor Proteins - metabolism
ISSN:1525-2191, 1525-2191
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Abstract Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA.
AbstractList Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA.Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA.
Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA.
Author Liu, Jie
Pei, Yao-Fei
Cheng, Jian
Liu, Xi-Qiang
Wu, Wei-Ding
Author_xml – sequence: 1
  givenname: Yao-Fei
  surname: Pei
  fullname: Pei, Yao-Fei
  organization: Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China
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  givenname: Jie
  surname: Liu
  fullname: Liu, Jie
  organization: Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China
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  givenname: Jian
  surname: Cheng
  fullname: Cheng, Jian
  organization: Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China
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  givenname: Wei-Ding
  surname: Wu
  fullname: Wu, Wei-Ding
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  organization: Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China. Electronic address: wu_weiding@163.com
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  email: 416095688@qq.com
  organization: Department of Hepatopancreatobiliary Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, People's Republic of China. Electronic address: 416095688@qq.com
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Snippet Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and...
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SubjectTerms Adult
Aged
Animals
Bile Duct Neoplasms - blood supply
Bile Duct Neoplasms - metabolism
Bile Duct Neoplasms - pathology
Cell Line, Tumor
Cholangiocarcinoma - blood supply
Cholangiocarcinoma - metabolism
Cholangiocarcinoma - pathology
Epithelial-Mesenchymal Transition
ErbB Receptors - metabolism
Female
Gene Silencing
Humans
Laminin - metabolism
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Middle Aged
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Signal Transduction
Tumor Suppressor Proteins - metabolism
Title Silencing of LAMC2 Reverses Epithelial-Mesenchymal Transition and Inhibits Angiogenesis in Cholangiocarcinoma via Inactivation of the Epidermal Growth Factor Receptor Signaling Pathway
URI https://www.ncbi.nlm.nih.gov/pubmed/31345467
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