Thomas R. Cox, Jan 2018
The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis.
Our recent review discussing the role of the extracellular matrix as a critical regulator of intracellular kinase signalling has just been published in Cell Adhesion & Migration
In this review, we summarise the interactions between ECM remodelling and major kinase activity in the context of cancer. In particular we highlight how post-translational cross-linking mediated by lysyl oxidase (LOX) catalyses the crosslinking of collagen fibres, essential for both fibrillar collagen deposition and increases in ECM stiffness. These ECM changes lead to altered intracellular kinase signalling, including key pathways such as FAK and SRC signalling pathways via integrin activation. This altered kinase activity influences focal adhesion assembly/disassembly and cell-to-cell contact, as well as regulating cell proliferation and cell survival, leading to changes in aggressiveness of cancer cells within a tumour. We finish by discussing the potential to target and uncouple this interaction as an emerging and promising approach in the treatment of cancer.
The extracellular matrix (ECM) is a master regulator of cellular phenotype and behaviour. It plays a crucial role in both normal tissue homeostasis and complex diseases such as cancer. The interplay between the intrinsic factors of cancer cells themselves, including their genotype and signalling networks; and the extrinsic factors of the tumour stroma, such as the ECM and ECM remodelling; together determine the fate and behaviour of cancer cells. As a consequence, tumour progression, metastatic spread and response to therapy are ultimately controlled by ECM-driven fine-tuning of intracellular kinase signalling. The ability to target and uncouple this interaction presents an emerging and promising potential in the treatment of cancer.
Skhinas JN and Cox TR. The interplay between extracellular matrix remodelling and kinase signalling in cancer progression and metastasis
Cell Adhesion & Migration (2018) | doi: 10.1080/19336918.2017.1405208
Extracellular Matrix; Remodelling; Kinase Signalling; Cancer; Metastasis; Lysyl Oxidase
This work was supported by NHMRC (APP1129766) and Susan G. Komen (CCR17483294).