Id1-induced inhibition of p53 facilitates endothelial cell migration and tube formation by regulating the expression of beta1-integrin
- 321 Downloads
The Id1 protein is critical for endothelial cell angiogenesis, and this function is particularly relevant to cancer development, cardiovascular disease, and wound healing. We hypothesized that Id1 enhanced migration and tubulogenesis by controlling the expression and function of p53. In this study, we examined cell migration following Id1 overexpression and silencing endothelial cells. The results showed that overexpression of Id1 enhanced cell migration and increased beta1-integrin expression, but inhibition of beta1-integrin blocked motility even in clones overexpressing Id1, suggesting that Id1 regulated motility through beta1-integrin. Further analysis revealed that p53, whose expression and distribution is regulated by Id1, was critical for cell migration, and may be involved in regulating the expression of beta1-integrin. Inhibiting p53 function using PFT-α, a functional inhibitor of p53, increased the expression of beta1-integrin and promoted cell migration even in Id1-silencing endothelial cells, demonstrating that the Id1 knockdowns induced inhibition of endothelial cell migration and the expression of beta1-integrin were controlled by p53. In addition, Id1–p53 pathway regulated the cytoskeleton formation and tubulogenesis. These results demonstrate that Id1-induced beta1-integrin expression in endothelial cells and the function of Id1 in cell migration and tubulogenesis are dependent on p53.
KeywordsId1 Tubulogenesis Migration p53 Beta1-integrin
Inhibitors of differentiation
Hypoxia inducible factor
Human umbilical vascular endothelial cells
- RPMI 1640
Roswell Park Memorial Institute 1640
Fetal bovine serum
Bovine serum albumin
This research program was supported by grants from the National Natural Science Foundation of China (30970721) and the Fundamental Research Funds for the Central Universities (CDJXS10 23 22 10).
- 8.Sun X, Li C, Zhuang C, Gilmore WC, Cobos E, Tao Y, Dai Z (2009) Abl interactor 1 regulates Src-Id1-matrix metalloproteinase 9 axis and is required for invadopodia formation, extracellular matrix degradation and tumor growth of human breast cancer cells. Carcinogenesis 30:2109–2116PubMedCrossRefGoogle Scholar
- 28.Sano M, Minamino T, Toko H, Miyauchi H, Orimo M, Qin Y, Akazawa H, Tateno K, Kayama Y, Harada M, Shimizu I, Asahara T, Hamada H, Tomita S, Molkentin JD, Zou Y, Komuro I (2007) p53-induced inhibition of Hif-1 causes cardiac dysfunction during pressure overload. Nature 446:444–448PubMedCrossRefGoogle Scholar