`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,` says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study.
TGF-beta regulates cell growth and specialisation, in particular during fetal development. In the context of tumor development, TGF-beta has a complicated role. Initially, it inhibits tumor formation because it inhibits cell division and stimulates cell death. At a late stage of tumor development, however, TGF-beta stimulates proliferation and metastasis of tumor cells and thereby accelerates tumor formation.
TGF-beta’s signalling mechanisms and role in tumor development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumor development.
Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta 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. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumor development and metastasis.