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Snail1 induced in breast cancer cells in 3D collagen I gel environment suppresses cortactin and impairs effective invadopodia formation

Authors
 Mi-Sook Lee  ;  Sudong Kim  ;  Baek Gil Kim  ;  Cheolhee Won  ;  Seo Hee Nam  ;  Suki Kang  ;  Hye-Jin Kim  ;  Minkyung Kang  ;  Jihye Ryu  ;  Haeng Eun Song  ;  Doohyung Lee  ;  Sang-Kyu Ye  ;  Noo Li Jeon  ;  Tai Young Kim  ;  Nam Hoon Cho  ;  Jung Weon Lee 
Citation
 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, Vol.1843(9) : 2037-2054, 2014 
Journal Title
 BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH 
ISSN
 0167-4889 
Issue Date
2014
MeSH
Actins/metabolism ; Animals ; Breast Neoplasms/enzymology ; Breast Neoplasms/metabolism* ; Breast Neoplasms/pathology* ; Cattle ; Cell Line, Tumor ; Cell Membrane/metabolism ; Cell Movement ; Cell Nucleus/metabolism ; Collagen Type I/pharmacology* ; Cortactin/genetics ; Cortactin/metabolism* ; Female ; Gels ; Humans ; JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors ; JNK Mitogen-Activated Protein Kinases/metabolism ; Matrix Metalloproteinase 14/metabolism ; Neoplasm Invasiveness ; Phosphoserine/metabolism ; Protein Transport ; Proto-Oncogene Proteins c-jun/metabolism ; Pseudopodia/drug effects ; Pseudopodia/metabolism* ; Signal Transduction ; Smad Proteins/metabolism ; Snail Family Transcription Factors ; Transcription Factors/metabolism* ; Transcription, Genetic ; Transforming Growth Factor beta1/metabolism ; Tumor Microenvironment/drug effects*
Keywords
3D collagen ; Cortactin ; Invasion ; JNK ; Snail1
Abstract
Although an in vitro 3D environment cannot completely mimic the in vivo tumor site, embedding tumor cells in a 3D extracellular matrix (ECM) allows for the study of cancer cell behaviors and the screening of anti-metastatic reagents with a more in vivo-like context. Here we explored the behaviors of MDA-MB-231 breast cancer cells embedded in 3D collagen I. Diverse tumor environmental conditions (including cell density, extracellular acidity, or hypoxia as mimics for a continuous tumor growth) reduced JNKs, enhanced TGFβ1/Smad signaling activity, induced Snail1, and reduced cortactin expression. The reduced JNKs activity blocked efficient formation of invadopodia labeled with actin, cortactin, or MT1-MMP. JNKs inactivation activated Smad2 and Smad4, which were required for Snail1 expression. Snail1 then repressed cortactin expression, causing reduced invadopodia formation and prominent localization of MT1-MMP at perinuclear regions. MDA-MB-231 cells thus exhibited less efficient collagen I degradation and invasion in 3D collagen I upon JNKs inhibition. These observations support a signaling network among JNKs, Smads, Snail1, and cortactin to regulate the invasion of MDA-MB-231 cells embedded in 3D collagen I, which may be targeted during screening of anti-invasion reagents.
Full Text
http://www.sciencedirect.com/science/article/pii/S0167488914001542
DOI
10.1016/j.bbamcr.2014.05.007
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kang, Suki(강숙희) ORCID logo https://orcid.org/0000-0002-9957-3479
Kim, Baek Gil(김백길) ORCID logo https://orcid.org/0000-0001-6270-1433
Cho, Nam Hoon(조남훈) ORCID logo https://orcid.org/0000-0002-0045-6441
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/99518
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