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TM4SF1 Promotes Metastasis of Pancreatic Cancer via Regulating the Expression of DDR1
- Source :
- Scientific Reports
- Publication Year :
- 2017
- Publisher :
- Nature Publishing Group, 2017.
-
Abstract
- Transmembrane-4-L-six-family-1(TM4SF1), a four-transmembrane L6 family member, is highly expressed in various pancreatic cancer cell lines and promotes cancer cells metastasis. However, the TM4SF1-associated signaling network in metastasis remains unknown. In the present study, we found that TM4SF1 affected the formation and function of invadopodia. Silencing of TM4SF1 reduced the expression of DDR1 significantly in PANC-1 and AsPC-1 cells. Through double fluorescence immuno-staining and Co-immunoprecipitation, we also found that TM4SF1 colocalized with DDR1 and had an interaction with DDR1. In addition, upregulating the expression of DDR1 rescued the inhibitory effects of cell migration and invasion, the expression of MMP2 and MMP9 and the formation and function of invadopodia when TM4SF1 silenced. In pancreatic cancer tissues, qRT-PCR and scatter plots analysis further determined that TM4SF1 had a correlation with DDR1. Collectively, our study provides a novel regulatory pathway involving TM4SF1, DDR1, MMP2 and MMP9, which promotes the formation and function of invadopodia to support cell migration and invasion in pancreatic cancer.
- Subjects :
- 0301 basic medicine
Oncology
medicine.medical_specialty
MMP2
Apoptosis
Biology
Article
Metastasis
03 medical and health sciences
0302 clinical medicine
Discoidin Domain Receptor 1
Cell Movement
Pancreatic cancer
Internal medicine
Cell Line, Tumor
medicine
Gene silencing
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Cell Proliferation
Regulation of gene expression
Multidisciplinary
Cell migration
medicine.disease
Neoplasm Proteins
Gene Expression Regulation, Neoplastic
Pancreatic Neoplasms
030104 developmental biology
Matrix Metalloproteinase 9
030220 oncology & carcinogenesis
Invadopodia
Cancer cell
Antigens, Surface
Podosomes
Cancer research
Matrix Metalloproteinase 2
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 20452322
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....adadde981665a8e1e6563af165e5794d
- Full Text :
- https://doi.org/10.1038/srep45895