New Signaling Molecule may Have a Role in Tumor Metastasis

The mechanism by which transforming growth factor (TGFβ) suppresses and stimulates tumor development has been studied by researchers and published in journal Science Signaling. "Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGFβ signals that stimulate tumor development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer," says Eleftheria Vasilaki, Postdoctoral Researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study.

The transforming growth factor β (TGFβ) regulates cell growth and specialization, in particular during fetal development. In the context of tumour development, TGFβ has a complicated role. Initially, TGFβ inhibits tumor formation because it inhibits cell division and stimulates cell death. At a late stage of tumor development, however, TGFβ stimulates proliferation and metastasis of tumour cells and thereby accelerates tumor formation.

TGFβ's signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, which are now being published in the current study in Science Signaling, explain part of the mechanism by which TGFβ switches from suppressing to enhancing tumor development.

Uppsala researchers, in collaboration with a Japanese research team, discovered that TGFβ, along with the oncoprotein Ras, which is often activated in tumors, affects members of the p53 family. The p53 protein plays a key role in regulating tumor development and is often altered - mutated - in tumors. TGFβ and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely ΔNp63, which in turn stimulates tumor development and metastasis.

Source-Eurekalert