Sir Run Run Shaw Hospital, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, China.
Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, China.
Int J Mol Sci. 2024 May 21;25(11):5585. doi: 10.3390/ijms25115585.
Anoikis, a form of apoptosis resulting from the loss of cell-extracellular matrix interaction, is a significant barrier to cancer cell metastasis. However, the epigenetic regulation of this process remains to be explored. Here, we demonstrate that the histone deacetylase sirtuin 6 (SIRT6) plays a pivotal role in conferring anoikis resistance to colorectal cancer (CRC) cells. The protein level of SIRT6 is negatively correlated with anoikis in CRC cells. The overexpression of SIRT6 decreases while the knockdown of SIRT6 increases detachment-induced anoikis. Mechanistically, SIRT6 inhibits the transcription of N-myc downstream-regulated gene 1 (), a negative regulator of the AKT signaling pathway. We observed the up-regulation of SIRT6 in advanced-stage CRC samples. Together, our findings unveil a novel epigenetic program regulating the anoikis of CRC cells.
失巢凋亡，一种由于细胞与细胞外基质相互作用丧失而导致的细胞凋亡形式，是癌细胞转移的一个重要障碍。然而，这一过程的表观遗传调控仍有待探索。在这里，我们证明了组蛋白去乙酰化酶沉默调节因子 6（SIRT6）在赋予结直肠癌（CRC）细胞抗失巢凋亡能力方面起着关键作用。SIRT6 的蛋白水平与 CRC 细胞中的失巢凋亡呈负相关。SIRT6 的过表达会降低，而 SIRT6 的敲低则会增加脱落诱导的失巢凋亡。在机制上，SIRT6 抑制 N-myc 下游调节基因 1 () 的转录，AKT 信号通路的负调节剂。我们观察到 SIRT6 在晚期 CRC 样本中的上调。总之，我们的研究结果揭示了一种新的表观遗传程序，调节 CRC 细胞的失巢凋亡。
