ArticleOncogene2014
A requirement for Nedd9 in luminal progenitor cells prior to mammary tumorigenesis in MMTV-HER2/ErbB2 mice.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Article
- NEDD9 sustains hexokinase expression to promote glycolysis.Oncogenesis · 2022Article
- Article
- BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- NEDD9 promotes oncogenic signaling, a stem/mesenchymal gene signature, and aggressive ovarian cancer growth in mice.Oncogene · 2018Article
- Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer.Journal of cancer research and clinical oncology · 2017Article
- A new role of SNAI2 in postlactational involution of the mammary gland links it to luminal breast cancer development.Oncogene · 2015Article
- Preclinical and clinical studies of the NEDD9 scaffold protein in cancer and other diseases.Gene · 2015Review
- Article
- New signaling pathways govern the host response to C. albicans infection in various niches.Genome research · 2015Article
- Article
- Nedd9 restrains renal cystogenesis in Pkd1-/- mice.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Prognostic factors related with survival in patients with pancreatic adenocarcinoma.World journal of gastroenterology · 2014Review
- Overexpression of Nedd9 is a prognostic marker of human gastric cancer.Medical oncology (Northwood, London, England) · 2014Article
- CAS proteins in health and disease: an update.IUBMB life · 2014Review
- NEDD9 depletion leads to MMP14 inactivation by TIMP2 and prevents invasion and metastasis.Molecular cancer research : MCR · 2014Article
- Cas proteins: dodgy scaffolding in breast cancer.Breast cancer research : BCR · 2014Review
- The Activation of the Sox2 RR2 Pluripotency Transcriptional Reporter in Human Breast Cancer Cell Lines is Dynamic and Labels Cells with Higher Tumorigenic Potential.Frontiers in oncology · 2014Article
- Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Overexpression of the NEDD9/HEF1/Cas-L scaffolding protein is frequent, and drives invasion and metastasis in breast, head and neck, colorectal, melanoma, lung and other types of cancer. We have examined the consequences of genetic ablation of Nedd9 in the MMTV-HER2/ERBB2/neu mouse mammary tumor model. Unexpectedly, we found that only a limited effect on metastasis in MMTV-neu;Nedd9(-/-) mice compared with MMTV-neu;Nedd9(+/+) mice, but instead a dramatic reduction in tumor incidence (18 versus 80%), and a significantly increased latency until tumor appearance. Orthotopic reinjection and tail-vein injection of cells arising from tumors, coupled with in vivo analysis, indicated tumors arising in MMTV-neu;Nedd9(-/-) mice had undergone mutational selection that overcame the initial requirement for Nedd9. To better understand the defects in early tumor growth, we compared mammary progenitor cell pools from MMTV-neu;Nedd9(-/-) versus MMTV-neu;Nedd9(+/+) mice. The MMTV-neu;Nedd9(-/-) genotype selectively reduced both the number and colony-forming potential of mammary luminal epithelial progenitor cells, while not affecting basal epithelial progenitors. MMTV-neu;Nedd9(-/-) mammospheres had striking defects in morphology and cell polarity. All of these defects were seen predominantly in the context of the HER2/neu oncogene, and were not associated with randomization of the plane of mitotic division, but rather with depressed expression the cell attachment protein FAK, accompanied by increased sensitivity to small molecule inhibitors of FAK and SRC. Surprisingly, in spite of these significant differences, only minimal changes were observed in the gene expression profile of Nedd9(-/-) mice, indicating critical Nedd9-dependent differences in cell growth properties were mediated via post-transcriptional regulation of cell signaling. Coupled with emerging data indicating a role for NEDD9 in progenitor cell populations during the morphogenesis of other tissues, these results indicate a functional requirement for NEDD9 in the growth of mammary cancer progenitor cells.
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