The role of tachykinins in gastrointestinal cancers

Tachykinins (TKs) belong to a group of neurotransmitters/neuropeptides that are widely distributed within the peripheral and central nervous system.This family shares the common carboxyl terminalsequence, -Phe-X-Gly-Leu-Met-NH2, where X is a variable amino acid. TKs exert their activity through three subtypes of transmembrane G-protein coupled receptors denoted NK1, NK2 and NK3. Different studies showed an increased expression of TKs and their receptors in tumor cells, which has multiple roles in proliferation, apoptosis and metastasis. Gastrointestinal cancer is one example in which TKs have a lot of effects in it. TKs play a Fundamental function in the development of malignancy in oral squamous cell carcinoma (OSCC). This claim is confirmed by the use of NK1- Receptor antagonists, which reduce and even inhibit the growth of OSCC. The increase of TACRs and TAC1 promoter hypermethylation can also cause malignancy, proliferation and progression of esophageal squamous cell carcinoma. The nuclear expression of TKs (Specially SP) is also shown to be increased significantly compared to healthy control which could induce proliferation of gastric cancer cells. In recent studies, high interactions between three genes (TAC1, TACR1, TACR2 ) were also found that may be involved in the development of colorectal cancer. Furthermore, studies on cholangiocarcinoma and hepatoblastoma indicate the critical role of SP/Nk1R signaling cascade in tumor malignancy. SP increases MMP2 expression by its effect on the NK1R and hence promotes migration of pancreatic cancer cell cluster to dorsal root ganglions and leads to metastasis. Therefore, it is concluded that TKs have a critical role in the progression of tumor cells and therapeutic strategies using NK1R antagonist might be a major step in reducing or inhibiting gastrointestinal cancer proliferation

کلیدواژه ها:

Colon Cancer ، Gastric Cancer ، Colorectal Cancer ، Cancer Diagnosis ، Cancer Risks