KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha
KiSS1 suppresses metastasis in human ovarian cancer via inhibition of protein kinase C alpha
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DOI：
10.1007/s10585-005-8186-4
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发表时间：
2005-09-01
影响因子：
4
通讯作者：
Xu, Y
中科院分区：
文献类型：
--
作者：
Jiang, Y;Berk, M;Xu, Y
转移是癌症治疗的重要目标，因为大多数癌症患者死于转移性疾病，而不是原发性疾病。KiSS 1已被鉴定为黑色素瘤和乳腺癌中的转移抑制基因。我们发现KiSS1在人类卵巢癌中也是一种转移抑制因子。KiSS 1在卵巢癌细胞中的过表达抑制由血清或溶血磷脂酸（LPA）诱导的细胞迁移和在软琼脂中的定殖，但不抑制细胞增殖，代表转移抑制基因的特征。此外，使用实验性转移小鼠模型，我们表明SKOV3卵巢癌细胞中KiSS 1的表达抑制了小鼠中> 50%的转移定植（P < 0.0001）。我们发现激活蛋白激酶C（PKC）可逆转KiSS 1诱导的约80%的细胞迁移抑制，而用shRNA下调PKC α可恢复KiSS 1的作用，这为抑制PKC α可能是KiSS 1作用的重要机制提供了证据。这些结果表明KiSS 1是卵巢癌的转移抑制因子，并可能成为治疗卵巢癌的潜在分子靶点。
Metastasis is a vital target for cancer treatment, since the majority of cancer patients die from metastatic, rather than the primary disease. KiSS1 has been identified as a metastasis suppressor gene in melanoma and breast carcinomas. We show here that KiSS1 is also a metastasis suppressor in human ovarian cancer. Overexpression of KiSS1 in ovarian cancer cells inhibits cell migration induced by serum or lysophosphatidic acid (LPA), and colonization in soft agar, but not cell proliferation, representing the characteristics of a metastasis suppressor gene. Furthermore, using an experimental metastatic mouse model, we show that expression of KiSS1 in SKOV3 ovarian cancer cells suppresses > 50% metastatic colonization in mice (P < 0.0001). We find that activating protein kinase C (PKC) reverses about 80% of the inhibited cell migration induced by KiSS1, while down-regulation of PKC alpha with shRNA restores KiSS1 effect, providing evidence that inhibiting PKC alpha may be an important mechanism of the effect of KiSS1. These results suggest that KiSS1 is a metastasis suppressor of ovarian cancer and may be a potential molecular target for the treatment.