KISS1 metastasis suppression and emergent pathways
KISS1 metastasis suppression and emergent pathways
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DOI：
10.1023/a:1022530100931
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Miele, ME
中科院分区：
文献类型：
--
作者：
Harms, JF;Welch, DR;Miele, ME
转移性疾病是癌症患者生存的最关键障碍。然而，相对知之甚少的复杂途径，管理与转移相关的复杂表型。KISS 1转移抑制基因在体内黑色素瘤和乳腺癌模型中均抑制转移。尽管KISS 1具有明确的生理活性，但其机制仍不清楚。最近对KISS 1的54个氨基酸肽（称为metastin或kisspeptin-54）及其同源G蛋白偶联受体（hOT 7T175、AXOR 12、GPR 54）的鉴定提供了额外的线索和研究途径。虽然研究已经将KISS 1与NF κ B调节的调节相关联，但是使用metastin及其受体的实验涉及MAP激酶途径，并且还表明自分泌、旁分泌和内分泌作用的潜力。对运动性、趋化性、粘附性和侵袭性的影响在不同的细胞系中均有记载，相互矛盾的观察结果需要解决。然而，越来越多的临床证据，特别是转移瘤中KISS 1的丢失，将KISS 1和转移蛋白受体表达与人类肿瘤进展相关。总之，数据证实了这些分子在转移调节中的作用。
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.