Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Daejeon, Republic of Korea.
Oncogene. 2021 Jan;40(2):384-395. doi: 10.1038/s41388-020-01517-3. Epub 2020 Nov 4.
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.
桩蛋白（Paxillin，PXN）是黏着斑复合物的关键组成部分，与癌症进展有关，但潜在机制尚不清楚。本研究旨在阐明 PXN 影响癌症生长和进展的机制，我们使用癌症患者数据、细胞系和原位小鼠模型来解决这些问题。我们证明了一种以前未被认识的机制，即核 PXN 通过转录调节 SRC 表达来增强血管生成。SRC 通过 NF-ĸB 激活增加 PLAT 的表达；PLAT 通过内皮细胞中的 LRP1 促进血管生成。在卵巢癌小鼠模型中沉默 PXN 可减少血管生成、肿瘤生长和转移。这些发现为 PXN 在调节肿瘤血管生成和生长中的作用提供了新的认识。
