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Abstract
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.

Affiliations

Kyunghee Noh #  1   2 , Duc-Hiep Bach #  1 , Hyun-Jin Choi  1   3 , Mark S Kim  1 , Sherry Y Wu  1 , Sunila Pradeep  1 , Cristina Ivan  4   5 , Min-Soon Cho  6 , Emine Bayraktar  1 , Cristian Rodriguez-Aguayo  4   5 , Santosh K Dasari  1 , Elaine Stur  1 , Lingegowda S Mangala  1   4 , Gabriel Lopez-Berestein  4   5 , Anil K Sood  7   8   9
1 Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
2 Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon, Republic of Korea.
3 Department of Obstetrics and Gynecology, Chung-Ang University College of Medicine, Seoul, Republic of Korea.
4 Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
5 Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
6 Department of Benign Hematology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
7 Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. asood@mdanderson.org.
8 Center for RNA Interference and Non-Coding RNA, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. asood@mdanderson.org.
9 Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. asood@mdanderson.org.
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