Cancer cell biology: mutated KRAS & reciprocal signalling
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Cancer cell biology: mutated KRAS & reciprocal signalling


Tumours contain lots of different cells. Apart from the cancer cells, a tumour can
also include immune cells and stromal fibroblasts. In pancreatic cancer a protein called KRAS
is often mutated. Healthy KRAS occasionally sends a message
that tells the cell to divide. When KRAS is mutated, it becomes hyperactive
and can’t switch off any more. This causes KRAS to transmit too many growth signals within the cancer cell. This is called cell-autonomous signalling. In addition to cell-autonomous signalling,
mutant KRAS can signal to nearby fibroblasts. Because fibroblasts use different signalling
pathways to cancer cells, they interpret and process signals in ways that cancer cells
cannot. This allows mutated KRAS in cancer cells to
change the behaviour of neighbouring fibroblast cells. This is called non-cell-autonomous signalling. Non-cell-autonomous signalling can cause fibroblasts
to produce unique signals of their own. These unique signals can then return to the
cancer cells. Back in the cancer cells, they activate new
signalling pathways that the cancer cells do not activate on their own. Because these signals start with mutant KRAS
in the cancer cell, travel through the fibroblasts and then back to the cancer cells, we call
this reciprocal signalling. So mutated KRAS can drive cell-autonomous
signalling in cancer cells. KRAS also drives non-cell-autonomous signalling
in the nearby fibroblasts. We now show that mutant KRAS can hijack nearby
fibroblasts to drive reciprocal signalling back in the cancer cells. Finding this important new way in which mutated
KRAS can promote cancer growth may provide new possibilities for therapeutic intervention.

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