p55PIK-PI3K stimulates angiogenesis in colorectal cancer cell by activating NF-κB pathway.
Vascular growth factor (VEGF) is an important mediator of angiogenesis. PI3K plays essential roles in angiogenesis; however, the mechanisms and specific functions of individual isoforms of PI3K members in tumor angiogenesis regulation are still not fully understood. In this study, we evaluate the role of p55PIK, a PI3K regulatory subunit encoded by PIK3R3 gene, in tumor angiogenesis. We reported that overexpression of p55PIK in cancer cells up-regulated HIF-1α expression and increased VEGF expression. Furthermore, overexpression of p55PIK increased tumor angiogenesis in vivo and in vitro. Moreover, data indicated enhanced HIF-1α expression by p55PIK-PI3K depended on its ability to activate NF-кB signaling pathways, especially to increase the phosphorylation of p65 subunits of NF-κB. Our study suggested that p55PIK-PI3K was essential in regulating cancer cell-mediated angiogenesis and contributed to tumor growth and that the p55PIK provides a potential and specific target for new anti-angiogenesis drug development.
Cancer Research Institute, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030, China.
Guihua
G
Wang
Cheng
C
Chen
Rui
R
Yang
Xiaonian
X
Cao
Senyan
S
Lai
Xuelai
X
Luo
Yongdong
Y
Feng
Xianmin
X
Xia
Jianping
J
Gong
Junbo
J
Hu
D015153:Blotting, Western; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000503:physiopathology*; D017931:DNA Primers / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D046228:Microarray Analysis; D016328:NF-kappa B / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D017931:DNA Primers; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; C523442:PIK3R3 protein, human