While previous research has found that transforming growth factor beta (TGF-beta) can both stimulate and suppress cancerous tumor growth and development, the mechanisms behind this were unknown. Now, researchers at Ludwig Institute for Cancer Research at Uppsala University have uncovered some of the details governing this process.
The Ludwig Institute for Cancer Research at Uppsala University has a 30-year history in the study of TGF-beta’s role in cell signaling and tumorigenesis. Only now have researchers identified some of the mechanisms responsible for TGF-beta’s switch from tumor suppression to tumor enhancing.
“Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumor development without knocking out the signals that inhibit tumor development, and that this can eventually be used in the fight against cancer,” said Eleftheria Vasilaki, postdoctoral researcher at Uppsala University. The results of the research were published in the journal, Science Signaling.
TGF-beta is most active during fetal development where it acts to regulate cell growth and differentiation. The cytokine also plays a complicated role when it comes to tumor growth and development.
In collaboration with a research team in Japan, Vasilaki and colleagues found that TGF-beta works alongside another oncoprotein, Ras, which is often overexpressed in cancer cells. The two proteins suppress p53 protein, which is a key regulator of tumor development.
The suppression of p53 works to enhance the effect of a related protein, delta-Np63, which acts to stimulate cancer development and tumor metastasis. These findings could provide researchers with a better understanding of tumorigenesis, and TGF-beta could become a valuable drug target for the development of cancer therapies.