NF-κB inducing kinase, a central signaling component of the non-canonical pathway of NF-κB, contributes to ovarian cancer progression.
NF-κB inducing kinase, a central signaling component of the non-canonical pathway of NF-κB, contributes to ovarian cancer progression.
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NF-κB诱导激酶是NF-κB非经典途径的中心信号传导成分，有助于卵巢癌的进展。
DOI：
10.1371/journal.pone.0088347
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yamaoka S
中科院分区：
文献类型：
--
作者：
Uno M;Saitoh Y;Mochida K;Tsuruyama E;Kiyono T;Imoto I;Inazawa J;Yuasa Y;Kubota T;Yamaoka S
卵巢癌是女性死亡的主要原因之一，迫切需要开发新的治疗方法。核因子-κB（NF-κB）在包括卵巢癌在内的几种类型的癌症中被组成性激活，并且已知其支持癌细胞的存活。然而，NF-κB在卵巢癌中持续活化的分子机制仍不清楚。我们在此报道，除了先前报道的经典激活，NF-κB在卵巢癌细胞中通过非经典途径被激活。RNA干扰介导的NF-κB诱导激酶（NIK）沉默可降低NF-κB2/p52 DNA结合活性、NF-κ B依赖性报告基因表达以及NF-κB靶基因表达。值得注意的是，锚定依赖性和非依赖性细胞生长受损的NIK-耗尽的细胞。在裸鼠异种移植试验中，NIK的耗尽也抑制肿瘤形成。这些结果表明，NIK在组成性NF-κB活化和卵巢癌细胞的进展中起关键作用，并表明NIK代表卵巢癌的有吸引力的治疗靶点。
Ovarian cancer is one of the leading causes of female death and the development of novel therapeutic approaches is urgently required. Nuclear factor-κB (NF-κB) is constitutively activated in several types of cancer including ovarian cancer and is known to support the survival of cancer cells. However, molecular mechanisms of persistent activation of NF-κB in ovarian cancer remain largely unknown. We report here that, in addition to the previously reported canonical activation, NF-κB is activated through the noncanonical pathway in ovarian cancer cells. RNA interference-mediated silencing of NF-κB inducing kinase (NIK), a central regulator of the noncanonical pathway, reduced the NF-κB2/p52 DNA binding activity and NF-κB-dependent reporter gene expression as well as NF-κB target gene expression. Notably, anchorage-dependent and -independent cell growth was impaired in NIK-depleted cells. Depletion of NIK also suppressed tumor formation in the nude mouse xenograft assay. These results indicate that NIK plays a key role in constitutive NF-κB activation and the progression of ovarian cancer cells and suggest that NIK represents an attractive therapeutic target for ovarian cancer.
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影响因子：
5.2
作者：
Fritz, Rafael D.;Radziwill, Gerald
通讯作者：
Radziwill, Gerald
影响因子：
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作者：
Asangani IA;Harms PW;Dodson L;Pandhi M;Kunju LP;Maher CA;Fullen DR;Johnson TM;Giordano TJ;Palanisamy N;Chinnaiyan AM
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通讯作者：
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影响因子：
14.9
作者：
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通讯作者：
KOURILSKY, P
影响因子：
20.3
作者：
Saitoh, Yasunori;Yamamoto, Norio;Yamaoka, Shoji
通讯作者：
Yamaoka, Shoji