Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
J Genet Genomics. 2022 Mar;49(3):181-184. doi: 10.1016/j.jgg.2021.10.005. Epub 2021 Nov 10.
Cancer metastasis, a process that primary tumor cells disseminate to secondary organs, is the most lethal and least effectively treated characteristic of human cancers. Kisspeptins are proteins encoded by the KISS1 gene that was originally described as a melanoma metastasis suppressor gene. Then, Kisspeptins were discovered as the natural ligands of the G-protein-coupled receptor 54 (GPR54) that is also called KISS1R. The KISS1/KISS1R signaling is essential to control GnRH secretion during puberty and to establish mammalian reproductive function through the hypothalamic-pituitary-gonadal (HPG) axis. Although KISS1 primarily plays a suppressive role in the metastasis progression in several cancer types, emerging evidence indicates that the physiological effect of KISS1/KISS1R in cancer metastasis is tissue context-dependent and still controversial. Here, we will discuss the epigenetic mechanism involved in the regulation of KISS1 gene expression, the context-dependent role of KISS1/KISS1R, prometastasis/anti-metastasis signaling pathways of KISS1/KISS1R, and the perspective anticancer therapeutics via targeting KISS1/KISS1R.
癌症转移，即原发性肿瘤细胞扩散到继发性器官的过程，是人类癌症最致命且治疗效果最差的特征。Kisspeptins 是由 KISS1 基因编码的蛋白质，最初被描述为黑色素瘤转移抑制基因。然后，Kisspeptins 被发现是 G 蛋白偶联受体 54（GPR54）的天然配体，也称为 KISS1R。KISS1/KISS1R 信号对于青春期 GnRH 分泌的控制以及通过下丘脑-垂体-性腺（HPG）轴建立哺乳动物生殖功能至关重要。尽管 KISS1 在几种癌症类型的转移进展中主要起抑制作用，但新出现的证据表明，KISS1/KISS1R 在癌症转移中的生理作用取决于组织背景，并且仍存在争议。在这里，我们将讨论参与 KISS1 基因表达调控的表观遗传机制、KISS1/KISS1R 的上下文相关作用、KISS1/KISS1R 的促转移/抗转移信号通路，以及通过靶向 KISS1/KISS1R 进行癌症治疗的前景。
