Open AccessThe hidden role of paxillin: localization to nucleus promotes tumor angiogenesis
Author(s) -
Kyunghee Noh,
Duc Hiep Bach,
Hyun Jin Choi,
Mark S. Kim,
Sherry Y. Wu,
Sunila Pradeep,
Cristina Ivan,
Min Soon Cho,
Emine Bayraktar,
Cristian Rodríguez-Aguayo,
Santosh K. Dasari,
Elaine Stur,
Lingegowda S. Mangala,
Gabriel López-Berestein,
Anil K. Sood
Publication year - 2020
Publication title -
oncogene
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.395
H-Index - 342
eISSN - 1476-5594
pISSN - 0950-9232
DOI - 10.1038/s41388-020-01517-3
Subject(s) - angiogenesis , biology , paxillin , metastasis , cancer research , tumor progression , cancer , microbiology and biotechnology , focal adhesion , signal transduction , genetics
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.