Boissan Mathieu, Poupon Marie-France, Lacombe Marie-Lise
Inserm, U680, Paris, F-75012, France.
Med Sci (Paris). 2007 Dec;23(12):1115-23. doi: 10.1051/medsci/200723121115.
Metastatic dissemination represents a leading cause of death in cancer patients. Elucidating the mechanisms of the metastatic process is therefore essential to control it. Since 1988, when the NME (NM23) gene was discovered, several genes specifically suppressing the metastatic potential of tumor cells, have been identified. These metastasis suppressor genes, which exhibit a reduced expression in metastatic tumor cells, are defined by their capacity to suppress metastatic dissemination in vivo without inhibiting primary tumor growth when transfected into metastatic cell lines and injected into experimental animals. Their decreased expression in a subset of human tumor cohorts is associated with a high metastatic potential, thus confirming the data obtained in experimental models. Most of these genes affect key signal transduction pathways, including mitogen-activated protein kinases, Rho-GTPases and G-protein-coupled receptors. These signaling categories control cell-cell and cell-matrix interactions, which are important in monitoring adhesion, invasion and migration properties of metastatic tumor cells. Reduced expression of metastasis suppressor genes is most often due to epigenetic mechanisms, suggesting that their re-expression could constitute a new anti-metastatic therapy. In this paper, we review the literature on metastasis suppressor genes, with a particular focus on NM23.
转移扩散是癌症患者死亡的主要原因。因此，阐明转移过程的机制对于控制转移至关重要。自1988年发现NME（NM23）基因以来，已经鉴定出几种特异性抑制肿瘤细胞转移潜能的基因。这些转移抑制基因在转移肿瘤细胞中表达降低，其定义是当转染到转移细胞系并注射到实验动物体内时，具有在不抑制原发性肿瘤生长的情况下抑制体内转移扩散的能力。它们在一部分人类肿瘤队列中的表达降低与高转移潜能相关，从而证实了在实验模型中获得的数据。这些基因中的大多数影响关键信号转导途径，包括丝裂原活化蛋白激酶、Rho-GTP酶和G蛋白偶联受体。这些信号类别控制细胞间和细胞与基质的相互作用，这对于监测转移肿瘤细胞的黏附、侵袭和迁移特性很重要。转移抑制基因的表达降低最常见于表观遗传机制，这表明它们的重新表达可能构成一种新的抗转移疗法。在本文中，我们综述了关于转移抑制基因的文献，特别关注NM23。
