Peter Ten Dijke: “TGF-beta receptors may be therapeutic targets in treatments to prevent metastasis

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The study of the molecular mechanisms that regulate the signaling pathways of transforming growth factor (TGF-beta) is the field of action of Peter Ten Djike and his research group at the University of Leiden, the Netherlands. Ten Djike explained their latest developments in a lecture in the seminar series IDIBELL on March 2.

TGF-beta is involved in the regulation of many cellular processes. With respect to tumors has been shown to have a dual function contradictory. On one hand, in the initial state induces programmed cell death, so that it has a suppressive function of tumor growth, but in more advanced phases promotes cell migration and invasion, and therefore the metastasis.

“We are interested in this second role of TGF-beta” explained Ten Djike “because most patients do not die from a primary tumor but for its expansion and metastasis to other body parts.” His group studies receptors involved in the signaling pathway of TGF-beta that induces proliferation “they are enzymes and molecules that can be targeted by therapeutic treatments to inhibit the final action of TGF-beta to promote metastasis.”

Ten Dijke works with different molecules that are potential targets. He talked about TRAF4 in breast cancer “is a negative regulator of the signaling pathway of TGF-beta. If we inhibit this enzyme, we are inhibiting migration, invasion, therefore metastasis, induced by TGF-beta in breast cancer cells”.

Another approach that is already in clinical trials involving a pharmaceutical company is the inhibition of angiogenesis (genesis of blood vessels needed for nutrition and growth of tumor cells) induced by TGF-beta. “Inhibiting ALK receptor 1 and getting an antiangiogenic effect that makes tumor cells can not grow or migrate.”

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