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TAp73 suppresses tumor angiogenesis through repression of proangiogenic cytokines and HIF-1α activity

2014; National Academy of Sciences; Volume: 112; Issue: 1 Linguagem: Inglês

10.1073/pnas.1421697112

1091-6490

Marina Stantic, Habib A. M. Sakil, Hanna Zirath, Trixy Fang, Gema Sanz, Alejandro Fernandez-Woodbridge, Ana V. Marín, Evelyn Susanto, Tak W. Mak, Marie Arsenian‐Henriksson, Margareta Wilhelm,

Angiogenesis and VEGF in Cancer

Significance Angiogenesis, the development of blood vessels within a solid tumor, is not only essential for primary tumor growth but also vital for tumor invasion and metastasis. The TP73 gene, a p53-family gene, encodes for both a tumor suppressor, TAp73, and an oncogene, ΔNp73. Here we report that TAp73 and ΔNp73 have opposing roles in tumor angiogenesis. Loss of TAp73 or upregulation of ΔNp73 leads to highly vascularized tumors and is found to correlate with increased angiogenesis in patients with breast cancer. Furthermore, we show that TAp73 suppress proangiogenic cytokines and HIF-1α protein accumulation and that this repression is unleashed on TAp73 loss or ΔNp73 up-regulation, thus further fuelling tumor development.