Scientists identify two protein pieces of the cancer puzzle

How cancer develops is a complex puzzle, involving untold moving parts and chemical reactions. Now, scientists have found how two of these pieces work together to prevent cancer forming, which could unlock new types of cancer treatments.

The protein at the heart of the new study is known as PP2A. It’s found in the cells of every living creature and plays an important role in removing phosphate groups from other proteins. This, previous work has found, makes it useful as a tumor suppressor.

But how exactly it performed that function remained a mystery. Scientists weren’t sure which specific proteins it was regulating, and which ones had an anti-cancer effect. Now, researchers from the University of Copenhagen, Dartmouth College and the Norris Cotton Cancer Center have identified one of these mechanisms.

A diagram demonstrating how PP2A and ADAM17 interact
A diagram demonstrating how PP2A and ADAM17 interact

University of Copenhagen

The culprit turned out to be an enzyme called ADAM17, which sits on the outer membrane of cells and acts like a pair of molecular scissors. It cleaves other proteins, which among other things can stimulate cell growth. As such, ADAM17 is known to stimulate some cancers, such as breast and bowel cancer.

The team found that PP2A turns off ADAM17, which in turn suppresses tumors. Although ADAM17 mostly sits on the outside of a cell, PP2A attacks the section that’s on the inside, removing its phosphate groups and inactivating it.

In tests in mice, the team successfully inhibited tumor growth by having PP2A bind to ADAM17.

The researchers say that the next steps involve checking whether it’s possible to use PP2A-activating substances to regulate ADAM17 activity. If so, it could open a new avenue for cancer treatment. The team will also investigate other proteins that PP2A might interact with.

The research was published in the EMBO Journal.

Source: University of Copenhagen

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