ATF4-dependent fructolysis fuels growth of glioblastoma multiforme.
Chao ChenZhenxing ZhangCaiyun LiuBin WangPing LiuShu FangFan YangYongping YouXinjian LiPublished in: Nature communications (2022)
Excessive consumption of fructose in the Western diet contributes to cancer development. However, it is still unclear how cancer cells coordinate glucose and fructose metabolism during tumor malignant progression. We demonstrate here that glioblastoma multiforme (GBM) cells switch their energy supply from glycolysis to fructolysis in response to glucose deprivation. Mechanistically, glucose deprivation induces expression of two essential fructolytic proteins GLUT5 and ALDOB through selectively activating translation of activating transcription factor 4 (ATF4). Functionally, genetic or pharmacological disruption of ATF4-dependent fructolysis significantly inhibits growth and colony formation of GBM cells in vitro and GBM growth in vivo. In addition, ATF4, GLUT5, and ALDOB levels positively correlate with each other in GBM specimens and are poor prognostic indicators in GBM patients. This work highlights ATF4-dependent fructolysis as a metabolic feature and a potential therapeutic target for GBM.
Keyphrases
- transcription factor
- endoplasmic reticulum stress
- induced apoptosis
- signaling pathway
- cell cycle arrest
- end stage renal disease
- blood glucose
- dna binding
- newly diagnosed
- chronic kidney disease
- ejection fraction
- poor prognosis
- physical activity
- machine learning
- genome wide
- type diabetes
- south africa
- gene expression
- papillary thyroid
- metabolic syndrome
- squamous cell carcinoma
- risk assessment
- long non coding rna
- dna methylation
- body mass index
- weight gain