CGRP Promotes the Migration and Invasion of Human Tongue Squamous Cell Carcinoma Cells through Activation of JNK Signaling Pathway

Objective: Increasing evidence indicates that neurogenesis in the cancer is a common phenomenon, which calls us attention to the role of substances released by nerve terminals in the development of cancer. Previous studies demonstrated that neuropeptides influence the migration of prostate cancer cell lines. The mitogen-activated protein kinases (MAPKs) are involved in the migration/invasion of cancer cells. Thus, the current study investigated the effects of calcitonin gene related peptide (CGRP) on the migration and invasion of tongue squamous cell carcinoma (SCC) cells and the potential role of MAPK signaling pathways. Methods: The effects of CGRP on the migration and invasion of human tongue SCC cells (TSCCA cell line) were detected by Transwell assay. The effects of CGRP on the phosphorylated expression of MAPKs including extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) of TSCCA cells were examined using Western Blot. The effects of inhibitors for ERK, p38 and JNK on the CGRP-induced migration and invasion of TSCCA cells were examined using Transwell assay. Results: CGRP was shown to promote the migration (P<0.0001) and invasion (P=0.0008) of TSCCA cells by Transwell assay. Western Blot results revealed that the expression of pERK (P=0.0007), pp38 (P=0.0425) and pJNK (P=0.0348) was increased in TSCCA cells at 1 h, 6 h and 24 h after CGRP treatment, respectively. JNK inhibitor SP600125, but not ERK inhibitor PD98059 and p38 inhibitor SB203580, attenuated CGRP-induced migration (P=0.0286) and invasion (P=0.0293) of TSCCA cells. Conclusion: CGRP promotes the migration and invasion of oral SCC cells, which may be through the activation of JNK signaling pathway.