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

Abstract

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.

THBS2, a microRNA‑744‑5p target, modulates MMP9 expression through CUX1 in pancreatic neuroendocrine tumors

“…Upregulation of CUX1 stimulated proliferation, tumor growth, resistance to apoptosis and angiogenesis in Pnet (8). In the present study, CUX1 functioned as a transactivator for MMP9 transcription and induced the proliferation of pNET cells (potentially through modulating the transcription of certain effectors, for example p21, FGF1, VAV2), which was consistent with previous studies (44)(45)(46).…”

The Association of Aberrant Expression of FGF1 and mTOR-S6K1 in Colorectal Cancer

“…The final score was the average of five random selected regions. It graded as follows: -(0), + (1-4), ++ (5-8) and +++ (9)(10)(11)(12). Samples with final scores ++ or +++ were graded positive, andor + as negative.…”

“…The expression level of FGF1 and FGFR1 in these cancers indicated that FGF1 induce the invasion and metastasis of tumor cells. In cancer cells, amplified FGF1 expression promotes the proliferation and migration ability of tumor cells (7)(8)(9)(10). However, its expression level in CRC tissues and its expression correlated with clinical indicators and survival, have not been fully elucidated (11).…”

A Bromodomain-Containing Protein 4 (BRD4) Inhibitor Suppresses Angiogenesis by Regulating AP-1 Expression

“…Recent studies indicate that angiogenesis is dysregulated in various pathological processes, leading to various diseases, including cancer, cardiovascular disease, inflammation, and obesity (Carmeliet and Jain, 2000;Carmeliet, 2003;Srivastava et al, 2018). It has been established that the abnormal formation of blood vessels is effective as a treatment for patients with cancer, chronic liver disease, cardiovascular disease or other diseases; therefore, using anti-angiogenic agents as inhibitors has become a major therapeutic strategy (Liao et al, 2014;Chen et al, 2018;Srivastava et al, 2018). Currently, several angiogenesis inhibitors that specifically target VEGF, VEGFR, or other specific genes that are involved in angiogenesis can prolong life expectancy in patients with advanced colon cancer and are now being investigated in clinical trials alone or in combination with conventional therapeutic approaches of both cancer and retinal disease (Hurwitz et al, 2004;Avery et al, 2006).…”