Harms John F, Welch Danny R, Miele Mary E
Jake Gittlen Cancer Research Institute, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Clin Exp Metastasis. 2003;20(1):11-8. doi: 10.1023/a:1022530100931.
Metastatic disease is the most critical impediment to cancer patient survival. However, comparatively little is known concerning the intricate pathways which govern the complex phenotypes associated with metastasis. The KISS1 metastasis suppressor gene inhibits metastasis in both in vivo melanoma and breast carcinoma models. Despite its clear physiological activity, the mechanism of KISS1 remains unclear. Recent identification of a 54 amino acid peptide of KISS1, termed metastin or kisspeptin-54, and its cognate G-protein coupled receptor (hOT7T175, AXOR12, GPR54) have provided additional clues and avenues of research. While studies have attributed KISS1 with modulation of NFkappaB regulation, experiments with metastin and its receptor implicate MAP kinase pathways and also suggest the potential of autocrine, paracrine and endocrine roles. Impacts on motility, chemotaxis, adhesion and invasion have each been documented in disparate cell lines and conflicting observations require resolution. Nevertheless, mounting clinical evidence, particularly the loss of KISS1 in metastases, correlates KISS1 and metastin receptor expression with human tumor progression. Together, the data substantiate roles for these molecules in metastasis regulation.
转移性疾病是癌症患者生存的最关键障碍。然而，对于控制与转移相关的复杂表型的复杂途径，我们了解得相对较少。KISS1转移抑制基因在体内黑色素瘤和乳腺癌模型中均能抑制转移。尽管其生理活性明确，但其作用机制仍不清楚。最近发现了KISS1的一种54个氨基酸的肽，称为metastin或kisspeptin-54，以及其同源G蛋白偶联受体（hOT7T175、AXOR12、GPR54），这为研究提供了更多线索和途径。虽然研究认为KISS1可调节核因子κB的调控，但对metastin及其受体的实验表明其涉及丝裂原活化蛋白激酶途径，并且还提示了自分泌、旁分泌和内分泌作用的可能性。在不同细胞系中均已记录到对运动性、趋化性、黏附和侵袭的影响，相互矛盾的观察结果需要解决。尽管如此，越来越多的临床证据，特别是转移灶中KISS1的缺失，将KISS1和metastin受体表达与人类肿瘤进展联系起来。总之，这些数据证实了这些分子在转移调控中的作用。
