EGFR/MET promotes hepatocellular carcinoma metastasis by stabilizing tumor cells and resisting to RTKs inhibitors in circulating tumor microemboli.
Shouyang SongZhen YuYajing YouChenxi LiuXiaoyu XieHuanran LvFeng XiaoQiang ZhuChengyong QinPublished in: Cell death & disease (2022)
The receptor tyrosine kinases (RTKs) family is well-recognized as vital targets for the treatment of hepatocarcinoma cancer (HCC) clinically, whereas the survival benefit of target therapy sorafenib is not satisfactory for liver cancer patients due to metastasis. EGFR and MET are two molecules of the RTK family that were related to the survival time of liver cancer patients and resistance to targeted therapy in clinical reports. However, the mechanism and clinical therapeutic value of EGFR/MET in HCC metastasis are still not completely clarified. The study confirmed that EGFR/MET was highly expressed in HCC cells and tissues and the phosphorylation was stable after metastasis. The expression of EGFR/MET was up-regulated in circulating tumor microemboli (CTM) to accelerate IL-8 production and resistance to the lethal effect of leukocytes. Meanwhile, highly expressed EGFR/MET effectively regulated the Ras/MAPK pathway and stabilized suspended HCC cells by facilitating proliferation and inhibiting apoptosis. Moreover, EGFR/MET promoted phosphorylation of hetero-RTKs, which was dependent on high-energy phosphoric acid compounds rather than their direct interactions. In conclusion, highly expressed EGFR/MET could be used in CTM identification and suitable for preventing metastasis of HCC in clinical practice.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- small cell lung cancer
- circulating tumor
- cell cycle arrest
- signaling pathway
- induced apoptosis
- clinical practice
- oxidative stress
- cell death
- transcription factor
- endoplasmic reticulum stress
- cell free
- pi k akt
- long non coding rna
- binding protein
- bone marrow
- cell proliferation
- peripheral blood
- papillary thyroid