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Notch1 destabilizes the adherens junction complex through upregulation of the Snail family of E-cadherin repressors in non-small cell lung cancer

Authors
 Arum Kim  ;  Eun Young Kim  ;  Eun Na Cho  ;  Hyung Jung Kim  ;  Se Kyu Kim  ;  Joon Chang  ;  Chul Min Ahn  ;  Yoon Soo Chang 
Citation
 Oncology Reports, Vol.30(3) : 1423-1429, 2013 
Journal Title
 Oncology Reports 
ISSN
 1021-335X 
Issue Date
2013
MeSH
Adherens Junctions/genetics ; Adherens Junctions/metabolism* ; Adherens Junctions/pathology ; Animals ; Blotting, Western ; Cadherins/genetics ; Cadherins/metabolism* ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Adhesion ; Cell Cycle ; Cell Proliferation ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism* ; Lung Neoplasms/pathology ; Mice ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptor, Notch1/genetics ; Receptor, Notch1/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction ; Snail Family Transcription Factors ; Transcription Factors/genetics ; Transcription Factors/metabolism* ; Tumor Cells, Cultured ; Wnt Proteins/genetics ; Wnt Proteins/metabolism* ; beta Catenin/genetics ; beta Catenin/metabolism
Keywords
Adherens Junctions/genetics ; Adherens Junctions/metabolism* ; Adherens Junctions/pathology ; Animals ; Blotting, Western ; Cadherins/genetics ; Cadherins/metabolism* ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carcinoma, Non-Small-Cell Lung/pathology ; Cell Adhesion ; Cell Cycle ; Cell Proliferation ; Humans ; Immunoenzyme Techniques ; Lung Neoplasms/genetics ; Lung Neoplasms/metabolism* ; Lung Neoplasms/pathology ; Mice ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Receptor, Notch1/genetics ; Receptor, Notch1/metabolism* ; Reverse Transcriptase Polymerase Chain Reaction ; Snail Family Transcription Factors ; Transcription Factors/genetics ; Transcription Factors/metabolism* ; Tumor Cells, Cultured ; Wnt Proteins/genetics ; Wnt Proteins/metabolism* ; beta Catenin/genetics ; beta Catenin/metabolism
Abstract
One of the critical steps driving cancer cell migration and metastasis is the repression of cell adhesion molecules resulting in loss of cell‑to-cell adhesion. Although interactions between Notch1 and components of the adherens junction complex have been suggested, little is known concerning the consequence of their interactions. In this study, we investigated the interaction between the Notch1 and the E‑cadherin/β‑catenin complex, its effect on the expression of adherens junction complex components and its influence on non-small cell lung cancer (NSCLC) cell proliferation. With progression of lung neoplastic lesions in LSL K-ras G12D mice, the expression of E‑cadherin was inhibited whereas that of Notch1 was increased with frequent nuclear localization, suggesting an inverse relationship between E‑cadherin and Notch1 expression with tumor progression. Transduction of the human Notch1 intracellular domain (N1ICD) into NSCLC cells inhibited expression of E‑cadherin and β‑catenin and induced changes in the localization of adherens junction molecules. The loss of E‑cadherin was mediated through upregulation of the Snail family of transcription factors, Snail and Slug. Experiments in which siRNA against E-cadherin was introduced into NSCLC cells revealed that N1ICD decreased the expression of β‑catenin in an E‑cadherin‑independent manner, leading to inhibition of markers of Wnt/β‑catenin signaling activation. Despite inhibition of Wnt/β‑catenin signaling in the N1ICD‑transduced cells, cells transduced with N1ICD showed no difference in cell cycle progression when compared with that of the control vector-transduced cells. In conclusion, Notch1 inhibited the expression of E‑cadherin through upregulation of the Snail family of transcriptional factors, resulting in inhibition of expression of β‑catenin and destabilization of adherens junctions.
Full Text
http://www.spandidos-publications.com/or/30/3/1423
DOI
10.3892/or.2013.2565
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Se Kyu(김세규)
Kim, Eun Young(김은영) ORCID logo https://orcid.org/0000-0002-3281-5744
Kim, Hyung Jung(김형중) ORCID logo https://orcid.org/0000-0003-2498-0683
Ahn, Chul Min(안철민)
Chang, Yoon Soo(장윤수) ORCID logo https://orcid.org/0000-0003-3340-4223
Chang, Joon(장준) ORCID logo https://orcid.org/0000-0003-4542-6841
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87288
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