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Peptide to interfere with the combination of tumor proteins c-SRC and TM4SF5

Korean researchers have proposed peptides (small pieces of protein) that will interfere with the binding between tumor proteins that trigger cell overgrowth and migration.

The Korea Research Foundation’s research team, led by Professor Lee Jung-won of Seoul National University and Professor Choi Sun-ui of Ewha Womans University, proposed a peptide to interfere with the combination of representative tumor proteins c-SRC and TM4SF5 involved in liver cancer.

The combination of these two proteins was well known to activate signals related to cell proliferation or migration, causing tumors.

In particular, these proteins were also known to be involved in chronic liver diseases where there were no suitable inhibitors and mechanisms were not fully identified.

Through molecular modeling and mutation research, the team has identified in detail where the cell membrane protein TM4SF5, which is highly expressed in liver cancer, binds with the tumor protein c-Src.

The C-tail site (C-terminus) of TM4SF5 combines with the inactivated c-Src present in the cytoplasm to bring c-SRC into the cell membrane and to activate c-SRC by combining it with dephosphorylate.

Furthermore, based on this, peptide fragments resembling C-tailed sites of TM4SF5 were designed to prevent the binding of the two tumor proteins. It was intended to prevent the binding of the two tumor proteins by snatching the actual TM4SF5 competition and c-SRC. In particular, it has included the peptide sequence of viruses that help cell infiltration so that practical competition can take place.

Putting this peptide piece into the tumor mouse model and the animal model in which metastatic cancer formation in the lungs resulted in decreased cancer formation and lung metastasis compared to the control group.

It is expected these molecular modeling and mutation studies will provide the foundation for the development of inhibitors that can prevent this interaction by identifying the site of tumor protein interaction in detail.

Source: https://pubmed.ncbi.nlm.nih.gov/34335982/

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