The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis
| Autor: | Emine Bayraktar, Sunila Pradeep, Mark Seungwook Kim, Anil K. Sood, Duc-Hiep Bach, Lingegowda S. Mangala, Hyun Jin Choi, Cristina Ivan, Min Soon Cho, Elaine Stur, Cristian Rodriguez-Aguayo, Kyunghee Noh, Gabriel Lopez-Berestein, Santosh K. Dasari, Sherry Y. Wu |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Cancer Research Angiogenesis Mice Nude Apoptosis Article Metastasis Focal adhesion Mice 03 medical and health sciences 0302 clinical medicine Biomarkers Tumor Tumor Cells Cultured Genetics medicine Animals Humans Gene silencing Molecular Biology Paxillin Cell Proliferation Cell Nucleus Ovarian Neoplasms Neovascularization Pathologic biology Cancer Prognosis medicine.disease Xenograft Model Antitumor Assays LRP1 Gene Expression Regulation Neoplastic Survival Rate src-Family Kinases 030104 developmental biology Tissue Plasminogen Activator 030220 oncology & carcinogenesis Disease Progression biology.protein Cancer research Female Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Oncogene |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/s41388-020-01517-3 |
| Popis: | Paxillin (PXN), a key component of the focal adhesion complex, has been associated with cancer progression, but the underlying mechanisms are poorly understood. The purpose of this study was to elucidate mechanisms by which PXN affects cancer growth and progression, which we addressed using cancer patient data, cell lines, and orthotopic mouse models. We demonstrated a previously unrecognized mechanism whereby nuclear PXN enhances angiogenesis by transcriptionally regulating SRC expression. SRC, in turn, increases PLAT expression through NF-ĸB activation; PLAT promotes angiogenesis via LRP1 in endothelial cells. PXN silencing in ovarian cancer mouse models reduced angiogenesis, tumor growth, and metastasis. These findings provide a new understanding of the role of PXN in regulating tumor angiogenesis and growth. |
| Databáze: | OpenAIRE |
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