The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis

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 p...

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Bibliographic Details
Published in:Oncogene 2021-01, Vol.40 (2), p.384-395
Main Authors: Noh, Kyunghee, Bach, Duc-Hiep, Choi, Hyun-Jin, Kim, Mark S., Wu, Sherry Y., Pradeep, Sunila, Ivan, Cristina, Cho, Min-Soon, Bayraktar, Emine, Rodriguez-Aguayo, Cristian, Dasari, Santosh K., Stur, Elaine, Mangala, Lingegowda S., Lopez-Berestein, Gabriel, Sood, Anil K.
Format: Article
Language:English
Subjects:
38/1
42/89
631/67/1517/1709
631/67/2328
Angiogenesis
Animal models
Animals
Apoptosis
Biomarkers, Tumor - genetics
Biomarkers, Tumor - metabolism
Cancer
Cell Biology
Cell Nucleus - metabolism
Cell Proliferation
Disease Progression
Endothelial cells
Female
Gene Expression Regulation, Neoplastic
Human Genetics
Humans
Internal Medicine
Localization
Medicine
Medicine & Public Health
Metastases
Mice
Mice, Nude
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - metabolism
Neovascularization, Pathologic - pathology
Oncology
Ovarian cancer
Ovarian Neoplasms - blood supply
Ovarian Neoplasms - genetics
Ovarian Neoplasms - metabolism
Paxillin
Paxillin - antagonists & inhibitors
Paxillin - genetics
Paxillin - metabolism
Prognosis
src-Family Kinases - genetics
src-Family Kinases - metabolism
Survival Rate
Tissue Plasminogen Activator - genetics
Tissue Plasminogen Activator - metabolism
Transcription
Tumor cell lines
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
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Description
Summary: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.
ISSN:0950-9232
1476-5594
1476-5594
DOI:10.1038/s41388-020-01517-3