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RSS FeedsIJMS, Vol. 24, Pages 12779: Experimental and Computational Studies Reveal Novel Interaction of Lymphocytes Antigen 6K to TGF-β Receptor Complex (International Journal of Molecular Sciences)

 
 

14 august 2023 11:37:25

 
IJMS, Vol. 24, Pages 12779: Experimental and Computational Studies Reveal Novel Interaction of Lymphocytes Antigen 6K to TGF-β Receptor Complex (International Journal of Molecular Sciences)
 


TGF-β signaling promotes migration, invasion, and distant colonization of cancer cells in advanced metastatic cancers. TGF-β signaling suppresses the anti-tumor immune response in a tumor microenvironment, allowing sustained tumor growth. TGF-β plays an important role in normal physiology; thus it is no surprise that the clinical development of effective and safe TGF-β inhibitors has been hampered due to their high toxicity. We discovered that increased expression of LY6K in cancer cells led to increased TGF-β signaling and that inhibition of LY6K could lead to reduced TGF-β signaling and reduced in vivo tumor growth. LY6K is a highly cancer-specific protein, and it is not expressed in normal organs except in the testes. Thus, LY6K is a valid target for developing therapeutic strategies to inhibit TGF-β signaling in cancer cells. We employed in vitro pull-down assays and molecular dynamics simulations to understand the structural determinants of the TGF-β receptor complex with LY6K. This combined approach allowed us to identify the critical residues and dynamics of the LY6K interaction with the TGF-β receptor complex. These data are critical in designing novel drugs for the inhibition of TGF-β in LY6K expressing cancer, induction of anti-tumor immune response, and inhibition of tumor growth and metastatic spread.


 
32 viewsCategory: Biochemistry, Biophysics, Molecular Biology
 
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