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

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 a...

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Published inJournal 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
LanguageEnglish
Published England John Wiley & Sons, Inc 01.10.2018
John Wiley and Sons Inc
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Summary: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.
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Chen and Zhou equally contributed to this study.
ISSN:1582-1838
1582-4934
DOI:10.1111/jcmm.13727