TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-β-catenin signaling.
TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-β-catenin signaling.
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DOI：
10.18632/aging.104163
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发表时间：
2020-12-02
期刊：
影响因子：
--
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Liu S;Tian Y;Zheng Y;Cheng Y;Zhang D;Jiang J;Li S
Wnt/β-catenin通路在多种生物学过程中发挥重要作用，包括细胞分化、增殖、迁移和胰岛素敏感性。最近的一项研究报道，DNA结合转录因子SIX 3在脊椎动物胚胎发育过程中是必需的，并且能够下调肺癌中Wnt/β-catenin通路的靶基因，表明Wnt/β-catenin活化的负调控。然而，SIX 3-Wnt/β-连环蛋白途径轴的调节仍然未知。我们测量了TRIM 27和SIX 3的表达，并研究了它们在肺癌组织样本中是否存在相关性。在此，我们发现E3泛素连接酶TRIM 27泛素化并降解SIX 3。TRIM 27诱导非小细胞肺癌（NSCLC）细胞增殖和转移，SIX 3显著抑制β-catenin、S100 P、TGFB 3和MMP-9的表达。此外，XAV 939是一种选择性β-连环蛋白介导的转录抑制剂，可抑制TRIM 27和SIX 3介导的NSCLC细胞增殖、迁移和侵袭。在临床上，癌症患者的肺组织样品显示TRIM 27表达增加和SIX 3表达减少。总之，这些数据表明TRIM 27作为癌基因通过SIX 3-β-连环蛋白信号传导调节NSCLC中的细胞增殖和转移。
The Wnt/β-catenin pathway plays vital roles in diverse biological processes, including cell differentiation, proliferation, migration, and insulin sensitivity. A recent study reported that the DNA-binding transcriptional factor SIX3 is essential during embryonic development in vertebrates and capable of downregulating target genes of the Wnt/β-catenin pathway in lung cancer, indicating negative regulation of Wnt/β-catenin activation. However, regulation of the SIX3-Wnt/β-catenin pathway axis remains unknown. We measured the expression of TRIM27 and SIX3 as well as investigated whether there was a correlation between them in lung cancer tissue samples. Herein, we found that the E3 ubiquitin ligase, TRIM27, ubiquitinates, and degrades SIX3. TRIM27 induces non-small cell lung cancer (NSCLC) cell proliferation and metastasis, and the expression of β-catenin, S100P, TGFB3, and MMP-9 were significantly inhibited by SIX3. Furthermore, XAV939 is a selective β-catenin-mediated transcription inhibitor that inhibited TRIM27- and SIX3-mediated NSCLC cell proliferation, migration, and invasion. Clinically, lung tissue samples of cancer patients showed increased TRIM27 expression and decreased SIX3 expression. Taken together, these data demonstrate that TRIM27 acts as an oncogene regulating cell proliferation and metastasis in NSCLC through SIX3-β-catenin signaling.
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