Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells.
Transcriptional induction of NF-κB-inducing kinase by E2F4/5 facilitates collective invasion of GBM cells.
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DOI：
10.1038/s41598-023-38996-9
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发表时间：
2023-08-11
影响因子：
4.6
通讯作者：
Sitcheran, Raquel
中科院分区：
文献类型：
--
作者：
Pflug, Kathryn M.;Lee, Dong W.;McFadden, Kassandra;Herrera, Linda;Sitcheran, Raquel
高级别胶质瘤，如多形性胶质母细胞瘤(GBM)，由于侵袭性强，预后极差。以往的研究表明，肿瘤坏死因子弱样因子(TWEEP)诱导非规范的NF-κB途径以依赖于NIK的方式促进κ细胞的侵袭性。虽然Nik的活性主要是在翻译后水平上调节的，但我们在这里表明，Nik(MAP3K14)在入侵细胞群体中在转录水平上上调，在最具侵袭性的细胞中观察到最高的Nik表达。高诱导Nik基因表达的GBM细胞表现出集体侵袭的特点，有利于邻近细胞的侵袭。此外，我们证明了E2F转录因子E2F4和E2F5直接调节NIK转录，并需要促进GBM细胞对TWEE的侵袭。总体而言，我们的发现表明，NIK的转录诱导促进了集体细胞的迁移和侵袭，从而促进了GBM的发病。
The prognosis of high-grade gliomas, such as glioblastoma multiforme (GBM), is extremely poor due to the highly invasive nature of these aggressive cancers. Previous work has demonstrated that TNF-weak like factor (TWEAK) induction of the noncanonical NF-κB pathway promotes the invasiveness of GBM cells in an NF-κB-inducing kinase (NIK)-dependent manner. While NIK activity is predominantly regulated at the posttranslational level, we show here that NIK (MAP3K14) is upregulated at the transcriptional level in invading cell populations, with the highest NIK expression observed in the most invasive cells. GBM cells with high induction of NIK gene expression demonstrate characteristics of collective invasion, facilitating invasion of neighboring cells. Furthermore, we demonstrate that the E2F transcription factors E2F4 and E2F5 directly regulate NIK transcription and are required to promote GBM cell invasion in response to TWEAK. Overall, our findings demonstrate that transcriptional induction of NIK facilitates collective cell migration and invasion, thereby promoting GBM pathogenesis.
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通讯作者：
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影响因子：
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作者：
Pippione, Agnese C.;Sainas, Stefano;Lolli, Marco L.
通讯作者：
Lolli, Marco L.