Cell: Zhou Dawang/Chen Lanfen's research group jointly published a paper revealing the important mechanism of glycogen accumulation and phase separation driving the initiation of liver cancer

Malignant tumors are a major disease threatening human life and health.

Malignant tumors are a major disease threatening human life and health.

On October 21st, the State Key Laboratory of Cell Stress Biology, the Cell Signal Network Collaborative Innovation Center, and the research group of Zhou Dawang and Chen Lanfen from the School of Life Sciences of Xiamen University jointly published the title Glycogen accumulation and phase separation drives liver tumor in Cell.

 

 

In this work, the author established a variety of mouse liver cancer models, analyzed early-stage liver tissues and combined with clinical samples of liver cancer, and found that excessive accumulation of glycogen is common in early liver tumor lesions and small tumors.

In this work, the author established a variety of mouse liver cancer models, analyzed early-stage liver tissues and combined with clinical samples of liver cancer, and found that excessive accumulation of glycogen is common in early liver tumor lesions and small tumors.

The findings of this work suggest that after the cancer cells in the initiation of early carcinogenesis absorb glucose, they may be stored in the cell as energy in the form of glycogen rather than metabolizing glucose in the form of anaerobic glycolysis

In order to explore the mechanism of glycogen accumulation in the tumor initiation, the authors used microdissection technology combined with RNA-Seq sequencing to compare and analyze the early tumor focus tissue and adjacent normal tissues, and found that glycogenolytic enzyme G6PC (glucose-6-phosphate) The expression of enzymes in the cancerous lesions decreased significantly, which may be an important factor in the accumulation of glycogen in early cancer foci

Clinically, inactivating mutations of various glycogenolytic enzymes, including G6PC, PYGL, etc.

This work further explains that the accumulated sugar phase separation causes the inactivation of the important tumor suppressor Hippo signaling pathway and activates the downstream proto-oncoprotein YAP, thereby driving the initiation of tumors

Recent studies have shown that the occurrence and development of various tumors is often accompanied by the inactivation of the Hippo pathway that inhibits cell carcinogenesis, but the specific mechanism is still unclear

 

 

In summary, this work found that early liver tumor cells use the extracted glucose to synthesize glycogen as energy storage, and inhibit the activity of the Hippo signaling pathway through liquid-liquid separation, thereby driving the occurrence and development of tumors

In summary, this work found that early liver tumor cells use the extracted glucose to synthesize glycogen as energy storage, and inhibit the activity of the Hippo signaling pathway through liquid-liquid separation, thereby driving the occurrence and development of tumors

This work reveals the pathogenesis of hepatomegaly and liver cancer caused by glycogen accumulation in the clinic, and provides a drug resistance mechanism for the potential survival of tumor cells under stress conditions for the phenomenon of glycogen accumulation in many types of tumor cells.

Doctoral students Liu Qingxu, Li Jiaxin, Zhang Weiji, Xiao Chen, and postdoctoral fellow Zhang Shihao (currently a professor at Anhui Medical University) from the School of Life Sciences of Xiamen University are the co-first authors of the paper.

The team of Professor Zhou Dawang and Professor Chen Lanfen intends to recruit several outstanding postdoctoral fellows/researchers to carry out research on tumor immunity .

Article link:

https://doi.

https://doi.
org/10.
1016/j.
cell.
2021.
10.
001

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