Publication date: February 2017
Source:Neoplasia, Volume 19, Issue 2
Author(s): Marcin Stawowczyk, Max D. Wellenstein, Sharrell B. Lee, Shira Yomtoubian, Anna Durrans, Hyejin Choi, Navneet Narula, Nasser K. Altorki, Dingcheng Gao, Vivek Mittal
Molecularly targeted therapies benefit approximately 15–20% of non-small cell lung cancer (NSCLC) patients carrying specific drug-sensitive mutations. Thus, there is a clinically unmet need for the identification of novel targets for drug development. Here, we performed RNA-deep sequencing to identify altered gene expression between malignant and non-malignant lung tissue. Matrix Metalloproteinase 14 (MMP14), a membrane-bound proteinase, was significantly up-regulated in the tumor epithelial cells and intratumoral myeloid compartments in both mouse and human NSCLC. Overexpression of a soluble dominant negative MMP14 (DN-MMP14) or pharmacological inhibition of MMP14 blocked invasion of lung cancer cells through a collagen I matrix in vitro and reduced tumor incidence in an orthotopic K-RasG12D/+p53−/− mouse model of lung cancer. Additionally, MMP14 activity mediated proteolytic processing and activation of Heparin-Binding EGF-like Growth Factor (HB-EGF), stimulating the EGFR signaling pathway to increase proliferation and tumor growth. This study highlights the potential for development of therapeutic strategies that target MMP14 in NSCLC with particular focus on MMP14-HB-EGF axis.
http://ift.tt/2ijKK2s
Σφακιανάκης Αλέξανδρος
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5 Άγιος Νικόλαος
Κρήτη 72100
00302841026182
00306932607174
alsfakia@gmail.com
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Matrix Metalloproteinase 14 promotes lung cancer by cleavage of Heparin-Binding EGF-like Growth Factor
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- Editorial Advisory Board
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- Understanding Resident Performance, Mindfulness, a...
- Facile synthesis of carbon dot and residual carbon...
- Clinical characterization of novel chromosome 22q1...
- Radiosurgical Target Distance from the Root Entry ...
- Curative brachytherapy for prostate cancer in Afri...
- Two female cases of focal dermal hypoplasia: One n...
- Langerhans cell histiocytosis with molluscum conta...
- Vitamin D3 derivatives, alone or in combination wi...
- Incidence of serum antibody titers against varicel...
- Short-term effect of scalpel debridement of planta...
- Psychological and Neural Mechanisms Associated wit...
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- The Influence of Alertness on the Spatial Deployme...
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- Development of a Multidimensional Assessment Tool ...
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- Continued Growth, A New Metric, Same High Quality!
- Cognitive–behavioral versus non-directive therapy ...
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- Acute renal dysfunction caused by nonsucrose intra...
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