Dipalmitoylphosphatidic acid inhibits breast cancer growth by suppressing angiogenesis via inhibition of the CUX1/FGF1/HGF signalling pathway

• Published in: Journal of cellular and molecular medicine Vol. 22; no. 10; pp. 4760 - 4770
• Main Authors: Chen, Jian, Zhou, Zijun, Yao, Yuying, Dai, Jianwei, Zhou, Dalei, Wang, Lijing, Zhang, Qian‐Qian
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.10.2018; John Wiley and Sons Inc
• Subjects: Angiogenesis; Animal models; Animals; Antineoplastic Agents - pharmacology; Breast cancer; Cancer therapies; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Chick Embryo; Chorioallantoic membrane; Chorioallantoic Membrane - blood supply; Chorioallantoic Membrane - drug effects; CUX1/FGF1/HGF signalling; dipalmitoylphosphatidic acid; Eggs; Embryos; Endothelial cells; Female; Fibroblast growth factor 1; Fibroblast Growth Factor 1 - genetics; Fibroblast Growth Factor 1 - metabolism; Gene Expression Regulation, Neoplastic; Genetic engineering; Growth factors; Hepatocyte growth factor; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Human Umbilical Vein Endothelial Cells - cytology; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Humidity; Inhibition; Laboratory animals; Mammary Neoplasms, Experimental - drug therapy; Mammary Neoplasms, Experimental - genetics; Mammary Neoplasms, Experimental - metabolism; Mammary Neoplasms, Experimental - pathology; Mice; Mice, Nude; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Neovascularization, Pathologic - prevention & control; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Nutrients; Original; Phosphatidic Acids - pharmacology; Phospholipids; Regulation; Repressor Proteins - genetics; Repressor Proteins - metabolism; Signal transduction; Signal Transduction - drug effects; Transcription; Transcription Factors; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - genetics; Triple Negative Breast Neoplasms - metabolism; Triple Negative Breast Neoplasms - pathology; Tumor Burden - drug effects; Tumors; Vascular endothelial growth factor; Xenograft Model Antitumor Assays; Xenografts; Yolk; Yolk sac; United States > US; China; dipalmitoylphosphatidic acid; breast cancer; CUX1/FGF1/HGF signalling; angiogenesis
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13727

Tumour growth depends on a continual supply of the nutrients and oxygen, which are offered by tumour angiogenesis. Our previous study showed that dipalmitoylphosphatidic acid (DPPA), a bioactive phospholipid, inhibits the growth of triple‐negative breast cancer cells. However, its direct effect on angiogenesis remains unknown. Our work showed that DPPA significantly suppressed vascular growth in the chick embryo chorioallantoic membrane (CAM) and yolk sac membrane (YSM) models. Meanwhile, tumour angiogenesis and tumour growth were inhibited by DPPA in the tumour tissues of an experimental breast cancer model, a subcutaneous xenograft mouse model and a genetically engineered spontaneous breast cancer mouse model (MMTV‐PyMT). Furthermore, DPPA directly inhibited the proliferation, migration and tube formation of vascular endothelial cells. The anti‐angiogenic effect of DPPA was regulated by the inhibition of Cut‐like homeobox1 (CUX1), which transcriptionally inhibited fibroblast growth factor 1 (FGF1), leading to the downregulation of hepatocyte growth factor (HGF). This work first demonstrates that DPPA directly inhibits angiogenesis in cancer development. Our previous work along with this study suggest that DPPA functions as an anti‐tumour therapeutic drug that inhibits angiogenesis.