Lysophosphatidic Acid Upregulates Recepteur D’origine Nantais Expression and Cell Invasion via Egr-1, AP-1, and NF-κB Signaling in Bladder Carcinoma Cells

International Journal of Molecular Sciences

Sen Lian¹  Yong Xia²  PhamNgoc Khoi³  TaekWon Kang³  Shinan Li³  DhirajKumar Sah³  ThiThinh Nguyen³  YoungDo Jung³  UngTrong Thuan³ 

[1] Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China;Institute of Precision Medicine, Jining Medical University, Jining 272067, China;Research Institute of Medical Sciences, Chonnam National University Medical School, Gwangju 501-190, Korea;

关键词: lysophosphatidic acid;    recepteur d’origine nantais;    bladder cancer;    egr-1;    ap-1;    nf-κb;   

DOI  :  10.3390/ijms21010304

来源: DOAJ

【 摘 要 】

Muscle invasive bladder carcinoma is a highly malignant cancer with a high mortality rate, due to its tendency to metastasize. The tyrosine kinase recepteur d’origine nantais (RON) promotes bladder carcinoma metastasis. Lysophosphatidic acid (LPA) is a phospholipid derivative, which acts as a signaling molecule to activate three high affinity G-protein coupled receptors, LPA1, LPA2, and LPA3. This in turn leads to cell proliferation and contributes to oncogenesis. However, little is known about the effects of LPA on invasive bladder cancer (IBC). In this study, we discovered that LPA upregulated RON expression, which in turn promoted cell invasion in bladder cancer T24 cells. As expected, we found that the LPA receptor was essential for the LPA induced increase in RON expression. More interestingly, we discovered that LPA induced RON expression via the MAPK (ERK1/2, JNK1/2), Egr-1, AP-1, and NF-κB signaling axes. These results provide experimental evidence and novel insights regarding bladder malignancy metastasis, which could be helpful for developing new therapeutic strategies for IBC treatment.

【 授权许可】

Unknown