The oncoprotein HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF
Open Access
- 24 January 2014
- journal article
- research article
- Published by Oxford University Press (OUP) in Carcinogenesis: Integrative Cancer Research
- Vol. 35 (5), 1144-1153
- https://doi.org/10.1093/carcin/bgu021
Abstract
Tumor angiogenesis plays an important role in the development of cancer. Previously, we reported that hepatitis B X-interacting protein (HBXIP) functioned as an oncoprotein in breast cancer. However, the role of HBXIP in angiogenesis in breast cancer remains poorly understood. In the present study, we show that the oncoprotein HBXIP plays crucial roles in the event. We observed that the expression levels of HBXIP were positively correlated with those of fibroblast growth factor 8 (FGF8) or vascular endothelial growth factor (VEGF) in clinical breast cancer tissues. Then, we demonstrated that HBXIP was able to upregulate FGF8 through activation of its promoter involving direct binding to cAMP response element-binding protein (CREB) in breast cancer cells and thereby increased its secretion. Strikingly, we identified another pathway that HBXIP upregulated FGF8 and VEGF through inhibiting miRNA-503, which directly targeted 3′ untranslated region of FGF8 or VEGF mRNA in the cells. Moreover, we revealed that HBXIP-induced FGF8 could upregulate VEGF expression through activating phosphoinositide 3-kinase (PI3K)/Akt/hypoxia-inducible factor 1-alpha (HIF1α) signaling and increase its secretion. In function, matrigel angiogenesis assay and hemoglobin content analysis uncovered that HBXIP-enhanced FGF8/VEGF boosted tumor angiogenesis and growth in breast cancer in vitro and in vivo in a paracrine/autocrine manner. Thus, we conclude that HBXIP enhances angiogenesis and growth of breast cancer through modulating FGF8 and VEGF. Our finding provides new insights into the mechanism of tumor angiogenesis in breast cancer. Therapeutically, HBXIP may serve as a novel target of tumor angiogenesis.Keywords
This publication has 44 references indexed in Scilit:
- MicroRNA-503 targets FGF2 and VEGFA and inhibits tumor angiogenesis and growthCancer Letters, 2013
- The oncoprotein HBXIP activates transcriptional coregulatory protein LMO4 via Sp1 to promote proliferation of breast cancer cellsCarcinogenesis: Integrative Cancer Research, 2013
- Ragulator Is a GEF for the Rag GTPases that Signal Amino Acid Levels to mTORC1Cell, 2012
- MicroRNA Destabilization Enables Dynamic Regulation of the miR-16 Family in Response to Cell-Cycle ChangesMolecular Cell, 2011
- β-arrestin1 mediates metastatic growth of breast cancer cells by facilitating HIF-1-dependent VEGF expressionOncogene, 2011
- miR-520b Regulates Migration of Breast Cancer Cells by Targeting Hepatitis B X-interacting Protein and Interleukin-8Published by Elsevier BV ,2011
- LMO4 is an essential mediator of ErbB2/HER2/Neu-induced breast cancer cell cycle progressionOncogene, 2009
- Significantly higher levels of vascular endothelial growth factor (VEGF) and shorter survival times for patients with primary operable triple-negative breast cancerAnnals of Oncology, 2009
- Lin-28B transactivation is necessary for Myc-mediated let-7 repression and proliferationProceedings of the National Academy of Sciences of the United States of America, 2009
- Angiogenesis in life, disease and medicineNature, 2005