The transforming growth factor-β (TGF-β) has a complex effect on the growth of tumors. In the early stages of tumor development, the protein factor suppresses the proliferation of cancer cells and induces their death. But it has a very different effect in the late stages of tumor development, when it instead stimulates the proliferation and metastasis of cancer cells. Why this should be the case has long been unclear. Now, a new study led by Ludwig Uppsala director Carl-Henrik Heldin and published in the journal Science Signaling provides some important insights on the matter.
The Ludwig Uppsala researchers, in collaboration with the research team of visiting professor and Ludwig Uppsala adjunct Kohei Miyazono of Tokyo University, discovered that TGF-β 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 suppressing tumor development and it is often deleteriously altered by mutation in tumors. Signaling by TGF-β, or through Ras, the Uppsala team found, suppresses the effects of mutated p53. This boosts the expression of another member of the p53 family, ΔNp63, which in turn stimulates tumor development and metastasis. The researchers report that ΔNp63 enhances the migration and invasion of cancer cells in cultures as well as in mice. They also show that elevated expression of ΔNp63 results in a relatively poor patient prognosis in a variety of cancers if the p53 encoded by tumor cells is mutated as well.
The original release about this study is available here.