ArticlePloS one2013
Oncogenic K-Ras and loss of Smad4 mediate invasion by activating an EGFR/NF-κB Axis that induces expression of MMP9 and uPA in human pancreas progenitor cells.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
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- Plasminogen deficiency suppresses pancreatic ductal adenocarcinoma disease progression.Molecular oncology · 2024Article
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- Combined Application of Patient-Derived Cells and Biomaterials as 3D In Vitro Tumor Models.Cancers · 2022Article
- Supply chain logistics - the role of the Golgi complex in extracellular matrix production and maintenance.Journal of cell science · 2022Review
- Neutrophils in Tumorigenesis: Missing Targets for Successful Next Generation Cancer Therapies?International journal of molecular sciences · 2021Review
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- Celecoxib combined with salirasib strongly inhibits pancreatic cancer cells in 2D and 3D cultures.International journal of medical sciences · 2020Article
- Alleviation of Ultraviolet-B Radiation-Induced Photoaging by a TNFR Antagonistic Peptide, TNFR2-SKE.Molecules and cells · 2019Article
- KRAS mutation and epithelial-macrophage interplay in pancreatic neoplastic transformation.International journal of cancer · 2018Article
- Mutational analysis of uterine cervical cancer that survived multiple rounds of radiotherapy.Oncotarget · 2018Article
- TUCR.454 inhabits metastasis in lung cancer cells.International journal of clinical and experimental pathology · 2018Article
- Cyclin E and FGF8 are downstream cell growth regulators in distinct tumor suppressor effects of ANXA7 in hormone-resistant cancer cells of breast versus prostate origin.Trends in cancer research · 2018Article
- miR-1, regulated by LMP1, suppresses tumour growth and metastasis by targeting K-ras in nasopharyngeal carcinoma.International journal of experimental pathology · 2015Article
- TLR9 ligation in pancreatic stellate cells promotes tumorigenesis.The Journal of experimental medicine · 2015Article
- Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro.Gene therapy · 2015Article
- Insights Into SMAD4 Loss in Pancreatic Cancer From Inducible Restoration of TGF-β Signaling.Molecular endocrinology (Baltimore, Md.) · 2015Article
- MicroRNA-30c-2-3p negatively regulates NF-κB signaling and cell cycle progression through downregulation of TRADD and CCNE1 in breast cancer.Molecular oncology · 2015Article
- Shikonin causes cell-cycle arrest and induces apoptosis by regulating the EGFR-NF-κB signalling pathway in human epidermoid carcinoma A431 cells.Bioscience reports · 2015Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Activating K-Ras mutations and inactivating mutations of Smad4 are two common genetic alterations that occur in the development and progression of pancreatic ductal adenocarcinomas (PDAC). To further study the individual and combinatorial roles of these two mutations in the pathogenesis of PDAC, immortalized human pancreas nestin postive cells (HPNE) were genetically modified by either expressing oncogenic K-Ras (HPNE/K-Ras), by shRNA knock down of Smad4 (HPNE/ShSmad4) or by creating both alterations in the same cell line (HPNE/K-Ras/ShSmad4). We previously found that expression of oncogenic K-Ras caused an increase in expression of EGFR and loss of Smad4 further enhanced the up regulation in expression of EGFR and that this increase in EGFR was sufficient to induce invasion. Here we further investigated the mechanism that links mutational alterations and EGFR expression with invasion. The increase in EGFR signaling was associated with up regulation of MMP9 and uPA protein and activity. Moreover, the increase in EGFR signaling promoted a nuclear translocation and binding of RelA (p65), a subunit of NF-κB, to the promoters of both MMP-9 and uPA. Treatment of HPNE/K-Ras/ShSmad4 cells with an inhibitor of EGFR reduced EGF-mediated NF-κB nuclear translocation and inhibitors of either EGFR or NF-κB reduced the increase in MMP-9 or uPA expression. In conclusion, this study provides the mechanism of how a combination of oncogenic K-Ras and loss of Smad4 causes invasion and provides the basis for new strategies to inhibit metastases.
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