Matrix and Metastasis
MATRIX AND METASTASIS
Targeting the Extracellular Matrix in Cancer Metastasis
Homeostasis of the extracellular matrix (ECM) is critical for correct organ and tissue function. Both the biochemical and biomechanical properties of the ECM contribute to modulating the behaviour of resident cells and are more than just passive bystanders. In tissue diseases such as cancer, the ECM undergoes significant change. These changes, driven by resident tumour cells, feed into the pathological progression of the disease. Understanding how the changing ECM facilitates tumour progression is an important step in the treatment and prevention of cancer.
Our research focuses on how ECM remodelling influences cancer progression, therapy response, and metastatic dissemination in solid tumours. Specifically we have shown that changes in the ECM are critical in modulating Src, FAK and Akt phosphorylation/activation, VEGF-driven angiogenesis, and nFATc1-mediated osteoclastogenesis.
Over the years we have shown the importance of aberrant ECM remodelling in cancer, including the role in ER-negative breast cancer bone metastasis through the generation of pre-metastatic niches; the importance of LOX and LOX activity in organ fibrosis, and how this enhances metastatic colonisation of cancer cells in these tissues; and how ECM remodelling and not only drives primary tumour growth, but can be used to stratify patients that will respond favourably to treatment with already approved clinical drugs, including bisphosphonates, and Src, Akt, VEGF and FAK inhibitors.
Altogether, our studies have contributed to increasing the current knowledge and understanding of the importance, and targeting potential, of lysyl oxidases, and ECM remodelling in cancer progression and metastasis. Several challenges still lie ahead, yet in the not-too distant future, our aim is to establish targeting of the extracellular matrix as a viable therapeutic approach in the treatment of solid cancers.