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

Oncogene 2021 Jan

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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.

Citation

Kyunghee Noh, Duc-Hiep Bach, Hyun-Jin Choi, Mark S Kim, Sherry Y Wu, Sunila Pradeep, Cristina Ivan, Min-Soon Cho, Emine Bayraktar, Cristian Rodriguez-Aguayo, Santosh K Dasari, Elaine Stur, Lingegowda S Mangala, Gabriel Lopez-Berestein, Anil K Sood. The hidden role of paxillin: localization to nucleus promotes tumor angiogenesis. Oncogene. 2021 Jan;40(2):384-395