SIRT6 Inhibits Anoikis of Colorectal Cancer Cells by Down-Regulating NDRG1.
Fengying LiWentao YuXiaoling ZhouJingyu HouYunyi GaoJun ZhangXiangwei GaoPublished in: International journal of molecular sciences (2024)
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 ( NDRG1 ), 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.
Keyphrases
- induced apoptosis
- oxidative stress
- cell cycle arrest
- signaling pathway
- ischemia reperfusion injury
- transcription factor
- extracellular matrix
- endoplasmic reticulum stress
- pi k akt
- cell death
- histone deacetylase
- diabetic rats
- stem cells
- quality improvement
- epithelial mesenchymal transition
- genome wide
- cell therapy
- small molecule