Researchers pinpoint protein 'boss' that controls gene
expression.
A protein
that determines whether breast cancer will spread and become deadly has been
found. Researchers say that the protein, which is found inside the nuclei of
cells, would be difficult and potentially dangerous to target with drugs. But
monitoring for the protein could help patients to know how dangerous their
cancer is before it spreads elsewhere, and help them
to decide which treatment to chose.
Because
breasts are not critical to survival, cancers that remain within breast tissue
do not kill the patient. But if the cancer cells break away from the original tumour, settle and start dividing elsewhere, these
secondary tumours can threaten the function of vital
organs.
Rather
like an invasive plant landing on an island, the circulating breast cancer cell
needs to evolve genetic changes to survive in a new environment. It has to find
a way to stick to a new type of cell or supporting structure, called a matrix,
and form links to surrounding cells, for instance.
Now a
protein has been found that changes the levels at which more than a thousand
genes are expressed in breast cancer cells, seemingly controlling whether
cancer cells will survive elsewhere. The protein is called SATB1. “All sorts of
molecular pathways that enable the cell to invade and inhabit a new
microenvironment are under the control of SATB1,” says Terumi
Kohwi-Shigematsu of the
Kohwi-Shigematsu and her colleagues had previously shown
that SATB1 acts as an architect inside the nuclei of cells, directing loops of
DNA to clump together. By changing the spatial arrangement of DNA, SATB1 can
alter the proteins surrounding some sections of the genome, and in changing
this 'casing' effectively turn some genes on and others off.
When the
researchers looked for SATB1 in breast cancer cells from more than 1,300
samples, they found a striking pattern. In almost all cases, the more SATB1
those cells contained, the more aggressive the tumour
was.
At
present, the test to see whether a cancer can spread to other organs, or
metastasize, involves looking for the cancer in the lymph nodes. But this
catches a tumour only in the act of spreading, rather
than beforehand. Crucially, in this study the link between high levels of SATB1
and aggressive tumours held for breast cancers that
had not yet spread to the lymph nodes.
This means
that the protein could be a good prognostic test for women with breast cancer.
“If we discover that this protein is present in the primary tumour,
we will have a good idea that the prognosis of this woman will be different and
maybe that will lead to a different choice of treatment,” says co-author Jose
Russo from the
To show
that SATB1 was both necessary and sufficient for breast cancer metastasis, the
team used a technique called RNA interference to remove it from highly
aggressive cancer cells in mice. This inhibited tumour
growth. They then added SATB1 to non-aggressive breast cancer cells in mice.
This caused those cells to alter the combinations of genes they expressed, and
made the cells resemble metastatic cells. The study
is published in the journal Nature 1.
“Researchers
have been describing changes to the DNA casing of large groups of genes in
cancer cells, but they have not understood what causes those changes,” says Frances
Shannon, a researcher at the Australian National University in Canberra. “This
study goes a step further by identifying what causes those changes," she
says. But, she adds, the next question is "what leads SATB1 levels to
rise?".
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