Mutations in a certain type of oncogene and tumor suppressor can collaborate to send cancerous cells into a malignant state, according to a study to be published online in Nature Structural & Molecular Biology. Mingxuan Xia and Hartmut Land examine the consequences of mutations in the oncogene Ras and the tumor suppressor p53.
Tumors are generally thought to arise due to the interaction of multiple mutations that alter protein function. Oncogenes, such as Ras, promote tumor formation when aberrantly activated through mutations. On the other hand, tumor suppressors, such as p53, have the opposite effect, in that they normally guard against aberrant cell growth.
A key event in the progression of cells to a malignant state during cancer progression is the abnormal acquisition of movement, which allows tumor cells to spread from their original location. A major regulator of cell movement is a factor called Rho. The team finds that when they experimentally activate Ras, Rho moves to its site of function at the cell membrane but is unable to trigger cell migration. However, when activated Ras is present with a p53 mutation that causes decreased p53 activity, membrane-localized Rho is now activated and cells acquire movement.
Hartmut Land (University of Rochester Medical Center, Rochester, NY, USA)
Abstract available online.
(C) Nature Structural & Molecular Biology press release.
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