MiR-22 downregulated the expression of NK1R-Tr and ERα to delay and weaken phosphorylation of ERK1/2 to inhibit proliferation and metastasis of breast cancer cells.
Increased sensitivity of metastatic breast carcinoma cells to NK1R and NK2R antagonists suggest potential therapeutic value of antagonists in metastatic disease.
Previous studies in breast cancer cell lines showed that truncated neurokinin receptor-1 (NK1R-Tr) was able to promote malignant transformation of breast cells, and NK1R-Tr may contribute to tumor progression and promote distant metastasis in human breast cancer.
Our in vitro and in vivo data showed that NK1R-FL expression was inversely associated with proliferation, invasiveness and metastasis of MDA-MB-231 cells, but overexpression of NK1R-Tr was able to promote malignant transformation of HBL-100 cells and NK1R-Tr may contribute to tumor progression and promote distant metastasis in human breast cancer.
Thus, 1) the SP/NK-1 receptor system plays an important role in the development of cancer, angiogenesis, and metastasis; 2) a common mechanism for cancer cell proliferation mediated by the SP/NK-1 receptor system occurs; 3) NK-1 receptor antagonists act as a broad-spectrum antitumoral agent; 4) the NK-1 receptor could be a new promising target in the treatment of cancer; 5) NK-1 receptor antagonists could improve cancer treatment--the development of antagonist molecules of the NK-1 receptor represents an important opportunity for exploiting these molecules as novel therapeutic agents.