Kinesin 18A expression: clinical relevance to colorectal cancer progression
Kinesin 18A expression: clinical relevance to colorectal cancer progression
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DOI：
10.1002/ijc.25916
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发表时间：
2011-12-01
影响因子：
6.4
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
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作者：
Nagahara, Makoto;Nishida, Naohiro;Mori, Masaki
Kif18A是分子马达蛋白驱动蛋白超家族的成员，是微管解聚酶和染色体聚集的关键调节剂。Kif18A在癌症进展中的作用尚未得到很好的定义。我们的假设是Kif18A在结直肠癌（CRC）的进展中起作用。为了研究Kif18A的表达，我们采用实时荧光定量PCR技术检测了113例原发性结直肠癌手术标本中Kif18A mRNA的表达。Kif18A在CRC中过表达，并且显著（p < 0.0001）高于正常结肠组织。Kif18A在结直肠癌中的过表达与临床病理因素如肿瘤分期（p < 0.0001）、淋巴管浸润（p = 0.001）、淋巴结转移（p = 0.01）、静脉浸润（p = 0.002）和腹膜播散（p = 0.02）显著相关，表明其在结直肠癌进展中起关键作用。在多变量分析中，Kif18A高表达与结直肠癌切除术后总生存率较差具有独立意义（p = 0.037）。为了证明Kif18A在CRC进展中的作用，我们进行了翻译和原位研究。利用对CRC细胞系的体外研究，我们评估了Kif18A在增殖、迁移和侵袭中的作用。与模拟转染的细胞相比，用Kif18A cDNA转染的CRC细胞表现出显著增强的迁移（p < 0.01）和侵袭（p = 0.018）。当用特异性小干扰RNA靶向Kif18A时，CRC细胞具有显著降低的增殖（p < 0.01）、迁移（p < 0.01）和侵袭（p < 0.05）。体外和翻译研究表明，Kif18A表达与转移事件有关，是CRC进展的重要因素。
Kif18A, a member of the kinesin superfamily of molecular motor proteins, is a microtubule depolymerase and a key regulator of chromosome congregation. Kif18A's role in cancer progression has not been well defined. Our hypothesis is that Kif18A has a role in the progression of colorectal cancer (CRC). To investigate this expression of Kif18A, mRNA was assessed by quantitative real-time PCR in 113 operative specimens of primary CRC. Kif18A was overexpressed and significantly (p < 0.0001) higher in CRC than in normal colon tissue. Kif18A overexpression in CRC significantly correlated with clinicopathologic factors such as tumor stage (p < 0.0001), lymphatic invasion (p = 0.001), lymph node metastasis (p = 0.01), venous invasion (p = 0.002) and peritoneal dissemination (p = 0.02), suggesting that it has a key role in CRC progression. In multivariate analysis, high Kif18A expression had independent significance for poorer overall survival after resection of CRC (p = 0.037). To demonstrate Kif18A's role in CRC progression, we performed translational and in situ studies. Using in vitro studies on CRC cell lines, we evaluated Kif18A's role in proliferation, migration and invasion. CRC cells transfected with Kif18A cDNA demonstrated significant enhanced migration (p < 0.01) and invasion (p = 0.018) compared to mock-transfected cells. When Kif18A was targeted with specific small interfering RNA, CRC cells had significantly reduced proliferation (p < 0.01), migration (p < 0.01) and invasion (p < 0.05). The in vitro and translational studies demonstrated that Kif18A expression is related to events of metastasis and is a significant factor for CRC progression.