ArticleOncogene2002
Oncogenic Ras/Her-2 mediate hyperproliferation of polarized epithelial cells in 3D cultures and rapid tumor growth via the PI3K pathway.
Article in Oncogene, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
35 citing papers in PubMed, 67 citations in OpenAlex.
- Review
- Artesunate inhibits epithelial-mesenchymal transition in non-small-cell lung cancer (NSCLC) cells by down-regulating the expression ofBioengineered · 2020Article
- Macrophages induce malignant traits in mammary epithelium via IKKε/TBK1 kinases and the serine biosynthesis pathway.EMBO molecular medicine · 2020Article
- An Integrative Systems Biology and Experimental Approach Identifies Convergence of Epithelial Plasticity, Metabolism, and Autophagy to Promote Chemoresistance.Journal of clinical medicine · 2019Article
- ΔNp63-driven recruitment of myeloid-derived suppressor cells promotes metastasis in triple-negative breast cancer.The Journal of clinical investigation · 2018Article
- Ras enhances TGF-β signaling by decreasing cellular protein levels of its type II receptor negative regulator SPSB1.Cell communication and signaling : CCS · 2018Article
- HMGB1 attenuates TGF-β-induced epithelial-mesenchymal transition of FaDu hypopharyngeal carcinoma cells through regulation of RAGE expression.Molecular and cellular biochemistry · 2017Article
- High-mobility group box 1 expression and lymph node metastasis in intrahepatic cholangiocarcinoma.World journal of gastroenterology · 2015Article
- Epithelial Mesenchymal Transition: a double-edged sword.Clinical and translational medicine · 2015Article
- Interleukin-like epithelial-to-mesenchymal transition inducer activity is controlled by proteolytic processing and plasminogen-urokinase plasminogen activator receptor system-regulated secretion during breast cancer progression.Breast cancer research : BCR · 2014Article
- [Advances in the molecular mechanisms and prognostic significance of EMT in non-small cell lung cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2014Review
- Epithelial-mesenchymal plasticity in carcinoma metastasis.Genes & development · 2013Review
- c-MYC-regulated miR-23a/24-2/27a cluster promotes mammary carcinoma cell invasion and hepatic metastasis by targeting Sprouty2.The Journal of biological chemistry · 2013Article
- Transmembrane/cytoplasmic, rather than catalytic, domains of Mmp14 signal to MAPK activation and mammary branching morphogenesis via binding to integrin β1.Development (Cambridge, England) · 2013Article
- The antidote effect of quinone oxidoreductase 2 inhibitor against paraquat-induced toxicity in vitro and in vivo.British journal of pharmacology · 2013Article
- Semaphorin-7a reverses the ERF-induced inhibition of EMT in Ras-dependent mouse mammary epithelial cells.Molecular biology of the cell · 2012Article
- A comparison of epithelial-to-mesenchymal transition and re-epithelialization.Seminars in cancer biology · 2012Review
- Annexin A1 attenuates EMT and metastatic potential in breast cancer.EMBO molecular medicine · 2010Article
- Nicotine induces cell proliferation, invasion and epithelial-mesenchymal transition in a variety of human cancer cell lines.International journal of cancer · 2009Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Carcinogenesis by oncogenic Ras and Her-2 involves enhanced proliferation of epithelial cells in vivo. However, hyperproliferation induced by these oncogenes, or their downstream pathways in vitro has mainly been studied in cultured, fibroblastic cell lines. Here, we demonstrate that oncogenic Ha-Ras or constitutively active Her-2 cause increased proliferation and cyclin D1 upregulation in fully polarized, mammary epithelial cells (EpH4), if cultivated as organotypic structures in three-dimensional collagen/matrigel matrices. Under standard culture conditions, however, these oncogenes failed to induce hyperproliferation. Using both specific low molecular weight inhibitors and Ras-effector-specific mutants, we dissected signaling pathways downstream of oncogenic Ras (PI3K, Mek1/MAPK) with respect to (i) hyperproliferation in collagen gels and tumorigenesis in mice and (ii) epithelial/mesenchymal transition (EMT). We show that the Ras-activated PI3K pathway is required to induce rapid tumor growth and enhanced proliferation of EpH4 cells in collagen gels, but fails to cause EMT in vitro and in vivo. On the other hand, Ras-dependent activation of the Mek1/MAPK pathway in EpH4 cells (previously shown to cause EMT and metastasis) did not induce hyperproliferation in collagen gels and caused only slow tumor growth. Our data thus indicate that Ras-dependent signaling through the PI3K- and MAPK pathways fulfil distinct, but complementary functions during carcinogenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.