Publication: The extracellular matrix as a key regulator of intracellular signalling networks

Thomas R. Cox, Jan 2019

The extracellular matrix as a key regulator of intracellular signalling networks

Our latest review in collaboration with Dr. David Croucher  and Dr. Dirk Fey on ‘The extracellular matrix as a key regulator of intracellular signalling networks‘ has just been published as part of a special series on ‘Translating the Matrix’ in the British Journal of Pharmacology.

Extracellular matrix interplay with MAPK-JNK Signalling

Computational model of the interplay between the ECM and drug activated MAPK‐JNK signalling network.

At their simplest, cells follow a set of rules governed by their genetic code. These rules, which are executed by the protein‐based signalling networks that the genes encode, control the assimilation of information and decision‐making processes that shape a cell’s response to their surroundings.

Under normal situations, each independent cellular decision results in the emergent phenomena of correct organ or tissue function.

Homeostasis of the extracellular matrix (ECM) is a fundamental regulator of cell and tissue behaviour, providing the majority of extracellular signalling cues that feed into these cellular decision‐making processes.

In many tissue diseases, aberrant ECM provides signalling cues that significantly alter cellular decision‐making processes, typically to the detriment of the organ or individual.

As yet, we still do not fully understand the importance and role of the ECM as a key signalling sub‐network in these processes, and only through a bottom‐up modelling approach to dissecting intracellular signalling, which includes the ever‐present ECM, will we begin to deepen our understanding of how to tackle these complex tissue diseases from a therapeutic perspective.

Abstract

The extracellular matrix (ECM) is a salient feature of all solid tissues within the body. This complex, acellular entity is composed of hundreds of individual molecules whose assembly, architecture and biomechanical properties are critical to controlling the behaviour and phenotype of the different cell types residing within tissues. Cells are the basic unit of life and the core building block of tissues and organs. At their simplest, they follow a set of rules, governed by their genetic code and effected through the complex protein signalling networks that these genes encode. These signalling networks assimilate and process the information received by the cell to control cellular decisions that govern cell fate. The ECM is the biggest provider of external stimuli to cells and as such is responsible for influencing intracellular signalling dynamics. In this review, we discuss the inclusion of ECM as a central regulatory signalling sub‐network in computational models of cellular decision making, with a focus on its role in diseases such as cancer.

Links

View abstract on PubMed
Read the full article on the journal website (Free Access)
Download the PDF version

Citation

Hastings JF et al. The extracellular matrix as a key regulator of intracellular signalling networks
British Journal of Pharmacology (2019) | doi: 10.1111/bph.14195

Key Words

Extracellular Matrix, Signalling Networks, Cancer, MAP Kinases

Funding

T.R.C. is supported by a Susan G. Komen for the Cure catalyst award and the National Health and Medical Research Council (NHMRC). J.N.S. is supported by the Cancer Institute NSW (CINSW). D.R.C. is a Cancer Institute NSW fellow (13/FRL/1‐02) and is supported by the NHMRC. J.F.H. is a recipient of an Australian Postgraduate Award.