Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells
Posted on 2020-03-11 - 04:35
Abstract Background High levels of the post-translational modification O-GlcNAcylation (O-GlcNAc) are found in multiple cancers, including bladder cancer. Autophagy, which can be induced by stress from post-translational modifications, plays a critical role in maintaining cellular homeostasis and regulating tumorigenesis. The impact of O-GlcNAcylation on autophagy in bladder cancer remains unclear. Here, we evaluate the change in autophagic activity in response to O-GlcNAcylation and explore the potential mechanisms. Methods O-GlcNAcylation levels in bladder cancer cells were altered through pharmacological or genetic manipulations: treating with 6-diazo-5-oxo-norleucine (DON) or thiamet-G (TG) or up- and downregulation of O-GlcNAc transferase (OGT) or O-GlcNAcase (OGA). Autophagy was determined using fluorescence microscopy and western blotting. Co-immunoprecipitation (Co-IP) assays were performed to evaluate whether the autophagy regulator AMP-activated protein kinase (AMPK) was O-GlcNAc modified. Results Cellular autophagic flux was strikingly enhanced as a result of O-GlcNAcylation suppression, whereas it decreased at high O-GlcNAcylation levels. Phosphorylation of AMPK increased after the suppression of O-GlcNAcylation. We found that O-GlcNAcylation of AMPK suppressed the activity of this regulator, thereby inhibiting ULK1 activity and autophagy. Conclusion We characterized a new function of O-GlcNAcylation in the suppression of autophagy via regulation of AMPK. Graphical abstract Blockage of O-linked GlcNAcylation induces AMPK dependent autophagy in bladder cancer cells.
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Jin, Lu; Yuan, Feng; Dai, Guangcheng; Yao, Qiu; Xiang, Han; Wang, Lixia; et al. (2020). Blockage of O-linked GlcNAcylation induces AMPK-dependent autophagy in bladder cancer cells. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.4889622.v1
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AUTHORS (9)
LJ
Lu Jin
FY
Feng Yuan
GD
Guangcheng Dai
QY
Qiu Yao
HX
Han Xiang
LW
Lixia Wang
BX
Boxin Xue
YS
Yuxi Shan
XL
Xiaolong Liu