脑肠肽Ghrelin-GHSR信号系统与肿瘤的关系

脑肠肽Ghrelin是一种含有28个氨基酸的生长激素释放肽,为生长激素促分泌素受体(growth hormone secretagogue recep-tor,GHSR)的内源性配体。Ghrelin及其功能性受体GHSR-1a广泛分布于中枢和外周组织。此外,在多种肿瘤组织和癌细胞中发现有Ghrelin及其功能性受体GHSR-1a的表达。我们的前期工作和目前的研究发现Ghrelin可与经典的功能性受体GHSR-1a或新型受体结合,通过激活多条信号转导通路,对肿瘤的生物学行为发挥重要的调控作用。因此,脑肠肽Ghrelin-GHSR信号系统可为肿瘤的临床诊断和预后评估发挥重要作用,并为肿瘤的分子治疗提供新靶点。

Study on the Relationship Between Ghrelin-GHSR Signaling Pathway and Tumor

Ghrelin is a 28-amino acid gut-brain peptide predominantly produced by the stomach, and has been identified as the endogenous ligand for the growth hormone secretagogue receptor (GHSR). Ghrelin and its receptor, GHSR-1a, are widely expressed in a number of organ systems. Apart from a potent GH-releasing action, more studies have described a number of additional functions for Ghrelin, including its ability to inhibit inflammatory cytokine expression, enhance memory retention, induce adiposity and exert prosur- vival effects on cardiomyocytes. In addition, our datas indicated that ghrelin inhibited apoptosis of neuronal cells from NO cytotoxicity via stimulating the induction of HSP70. These results demonstrated that activation of signaling transduction was not only mediated by GHSR-1a but also a new receptor of Ghrelin. Recent studies showed that Ghrelin and GHSR-1a were highly expressed in the human can- cer cell lines, hyperplastic and neoplastic tissues. In vitro, Ghrelin could regulate proliferation and invasiveness of tumor cells. Moreover, acylated and des-acylated Ghrelin could inhibit DNA synthesis and proliferation of the cancer cell lines through binding to a novel, as yet unidentified receptor. This article reviewed the construction and function of Ghrelin, evaluated the role of Ghrelin-GHSR signaling trans- duction for tumor formation and regulation. We anticipated that Ghrelin-GHSR system could serve as the important target for diagnosis marker, prognostic significance and therapeutic strategy in tumors.