Scientists discover motion protein promotes drug production
regions of a cell, a process crucial for the cellular motility,
which could form a basis for producing a drug that could force
tumour cells to express this protein, preventing cancers from
spreading.
Understanding how actin synthesis is spatially regulated in motile cells could lead to new cancer therapies.
"In cancer, we know that expression of ZBP1 correlates with benign tumours, while suppression of ZBP1 is associated with metastasis, when motile cancer cells break off from the primary tumour and invade other areas of the body," said Dr Robert Singer, co-lead researcher.
Singer and Dr Stefan Huettelmaier, along with their research team focused on migrating fibroblast cells important in wound healing.
To move towards a wound, these cells manufacture the protein actin, which polymerises into long filaments that push the cell's membrane outward to form protrusions.
This new study revealed that not only does ZBP1 bind to actin messenger RNA and guide it to the cell's periphery, but it also helps regulate where in the cell the messenger RNA is translated into actin.
"The ZBP1 bound to actin's messenger RNA acts like a lock to prevent it from being translated into protein before reaching its destination," said Dr Singer.
"On arriving at the cell periphery, the messenger RNA/ZBP1 complex encounters an enzyme, the protein kinase Src, which is active only in that part of the cell."
Src adds a phosphate group to ZBP1 close to where it binds to messenger RNA, and this phosphorylation reaction detaches ZBP1 from the actin messenger RNA-unlocking the messenger RNA.
It can now be translated into the actin protein that makes cell movement possible.
The team's previous work showed how newly formed actin messenger RNA molecules find their way to the cell's periphery.
A protein called ZBP1 binds to the messenger RNA and "escorts" it out of the fibroblast nucleus and into the cytoplasm.
On reaching the cell's periphery, the messenger RNA is translated into actin protein responsible for cell motility.
The study appears in the November 24 issue of the journal Nature.
