Matrix and Metastasis

Targetting 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.

Selected Publications

A full list of publications is available at www.matrixandmetastasis.com/publications


The Role of Lysyl Oxidase, the Extracellular Matrix and the Pre-Metastatic Niche in Bone Metastasis
Gartland A, Erler JT and Cox TR
Journal of Bone Oncology (2016)

Fibrosis and Cancer: Partners in Crime or Opposing Forces? 
Cox TR
# and Erler JT#
Trends In Cancer
 (2016)
#Corresponding Author

Nuclear expression of lysyl oxidase enzyme is an independent prognostic factor in rectal cancer patients
Liu N, Cox TR, Cui W, Adell G, Holmlund B, Ping J, Jarlsfelt I, Erler JT, Sun XF
Oncotarget (2016)

Lysyl Oxidase, a Targetable Secreted Molecule Involved in Cancer Metastasis
Cox TR#, Gartland A, Erler JT
Cancer Research (2016)
#Corresponding Author

Dataset for the proteomic inventory and quantitative analysis of the breast cancer hypoxic secretome associated with osteotropism
Cox TR#*, Schoof EM*, Gartland A, Erler JT, Linding R#
Data In Brief (2015)
*First authors contributed equally #Corresponding Author

Kinome-wide Decoding of Network Attacking Mutations Rewiring Cancer
Creixell P, Schoof EM, Simpson CD, Longden J, Miller CJ, Lou HJ, Perryman L, Cox TR, Zivanovic N, Palmeri A, Wesolowska-Andersen A, Helmer-Citterich M, Ferkinghoff-Borg J, Itamochi H, Bodenmiller B, Erler JT, Turk BE, Linding R
Cell (2015)

Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis
Madsen CD, Pedersen JT, Venning FA, Singh LB, Moeendarbary E, Charras G, Cox TR, Sahai E, Erler JT
EMBO Reports (2015)

The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase
Cox TR
, Rumney RMH, Schoof EM, Perryman L, Høye AM, Agrawal A, Bird, D, Ab Latif N, Forrest H, Evans HR, Huggins ID, Lang G, Linding R, Gartland A, Erler JT
Nature (2015)

Molecular pathways: connecting fibrosis and solid tumor metastasis
Cox TR# and Erler JT# 
Clinical Cancer Research
 (2014)
#Corresponding Author

LOX-mediated collagen crosslinking is responsible for fibrosis-enhanced metastasis
Cox TR, Bird D, Baker AM, Barker HE, Ho MW, Lang G, Erler JT
Cancer Research (2013)

Lysyl oxidase plays a critical role in endothelial cell stimulation to drive tumor angiogenesis
Baker AM, Bird D, Welti J, Gourlaouen M, Lang G, Murray G, Reynolds AR, Cox TR, Erler JT
Cancer Research (2013)

The rationale for targeting the LOX family in cancer
Barker HE*, Cox TR* and Erler JT 
Nature Reviews Cancer
 (2012)
*First authors contributed equally to this work

Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK
Baker AM, Lang G, Bird D, Cox TR*, Erler JT*
Oncogene (2012)
*Senior authors contributed equally

Remodeling and homeostasis of the extracellular matrix: implications for fibrotic diseases and cancer
Cox TR and Erler JT
Disease Models and Mechanisms (2011)

The Role of Lysyl Oxidase in SRC-Dependent Proliferation and Metastasis of Colorectal Cancer
Baker AM, Cox TR, Bird D, Lang G, Murray GI, Sun XF, Southall SM, Wilson JR, Erler JT
Journal of the National Cancer Institute (2011)

Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche
Erler JT, Bennewith KL, Cox TR, Lang G, Bird D, Koong A, Le QT, Giaccia AJ
Cancer Cell (2009)


More Garvan Publications

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In the News

Group Leader

Dr Thomas Cox


Diseases We Research
Breast Cancer
Bowel Cancer

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