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

• Published in: Oncogene Vol. 40; no. 2; pp. 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: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 14.01.2021; Nature Publishing Group
• Subjects: 38/1; 42/89; 631/67/1517/1709; 631/67/2328; Angiogenesis; Animal models; Animals; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Cancer; Carcinogenesis; Carrier proteins; Cell Biology; Cell Nucleus - metabolism; Cell Proliferation; Disease Progression; Endothelial cells; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic aspects; Health aspects; Human Genetics; Humans; Internal Medicine; Localization; Medicine; Medicine & Public Health; Metastases; Mice; Mice, Nude; Neovascularization; 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; United States
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/s41388-020-01517-3

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.