Defining the function of the interleukin-11 signalling complex

Defining the function of the interleukin-11 signalling complex

Details of project

Interleukins are cytokines that interact with receptors on target cells to trigger the activation of numerous pathways that regulate tissue homeostasis. Deregulated cytokine signalling occurs in a number of pathologies, including cancer.

IL-11 is a cytokine that, by binding to its specific receptor IL-11R, triggers intracellular signalling that activates the transcription factor STAT3. STAT3 has been implicated in the maintenance of a tumour-promoting, inflammatory microenvironment, and persistent STAT3 activation is a feature of many human cancers of both haematopoietic and epithelial origin.

We were the first to solve the structure of the IL-11 ligand, however, our understanding of the details of the IL-11 signalling machinery remains rudimentary. We recently identified mutations in components of the human IL-11 signalling complex and aim to characterise how these impact on the structure and function of this signalling pathway in different diseases. This will establish novel platforms for interventions that are likely to be translated to new treatments.

About our research group

Traditionally, elevated IL-6 (a cytokine related to IL-11) has been linked to aberrant STAT3 activation in cancers. However, we have recently shown that IL-11, but not IL-6, correlates with elevated STAT3 activation in human colorectal cancers. Furthermore, we have shown that both genetic ablation of IL-11R and pharmacological antagonism of IL-11 signalling can reduce tumour burden. We are interested in understanding why IL-11 plays a dominant role in promoting cancer progression.

 

Interleukin-11 signalling complex

Researchers:

Dr Tracy Putoczki

Tracy Putoczki
Dr
Tracy
Putoczki
Laboratory Head

Project Type:

Dr Tracy Putoczki working in the lab

A signalling molecule called interleukin-11 is a potential new target for anti-cancer therapies