Staying in place of cancer is not terrible, cancer deaths are mostly due to the spread of the disease to the important organs, this process is called cancer metastasis. Recently, two groups of researchers from Tongji University and Xiamen University discovered the different roles of two proto-oncogenes in tumor metastasis: The first study found that the oncogene Myc not only inhibited tumor infiltration, but also regulated the normal development . The second study indicated that c-Src, a proto-oncogene, promotes the mechanism of tumorigenesis and metastasis by phosphorylating the rate-limiting hexokinase (HK) in glycolysis.
The two results are published in Oncogene and Nature Communications, respectively.
Tumor migration is the main cause of cancer death, proven molecular mechanism of tumor migration is the key to prevention and treatment of cancer. Myc, an important proto-oncogene, is highly expressed in most human cancers and is closely related to tumorigenesis. However, its role in tumor cell invasion and migration is still controversial.
Researchers at Tongji University used the Drosophila melanogaster to establish an animal model of tumor migration, and carried out a large-scale genetic screening, and found that Myc can not only inhibit tumor infiltration, but also regulate the normal development of cell migration. It was found that Myc and Max form dimers, which act as transcription factors in the regulatory region of the puc gene and activate the expression of puc, thereby inhibiting JNK signaling pathway-mediated cell migration and tumor infiltration. Expression of the human homologue cMyc in Drosophila can also effectively inhibit cell migration and tumor infiltration, demonstrating that this function of Myc is highly conserved in evolution. In addition, the researchers in vitro cultured human lung cancer cell PC9 further confirmed that overexpression of cMyc can down-regulate JNK signaling pathway and slow down the migration of lung cancer cells; the contrary, knocking down cMyc is up-regulating JNK signaling pathway and promote tumor cell migration.
This study not only reveals the Myc cell migration and tumor infiltration of the regulatory mechanism, but also for the treatment of Myc-related cancer provides a theoretical basis.
Another study found that c-Src binds to HK at the same time as activated, and phosphorylates tyrosine 732 site of type 1 hexokinase (HK1) and Tyrosine of type II hexokinase (HK2) 686 sites. Phosphorylation led to a change in the conformation of HK, enhanced its affinity for glucose, and activated its catalytic activity. Activation of the HK so that a large number of glucose is taken into the 6-phosphate glucose, and promote glycolysis. In-depth studies have shown that c-Src phosphorylation of HK can promote tumor formation and metastasis. The phosphorylation of HK1-Y732 in colorectal cancer and lung cancer was significantly higher than that in primary tumor, indicating that the phosphorylation of HK1-Y732 could be used as a reference for the treatment and prognosis evaluation of related tumors. This study not only reveals a new mechanism of c-Src to promote tumorigenesis and metastasis, but also provides a theoretical basis for treatment and prognosis evaluation of related tumors.
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