Thomas R. Cox, Sep 2016
The BSMB, formerly known as the British Connective Tissue Society (BCTS) is a learned society of professional scientists with an interest in the Extracellular Matrix (ECM) in both health and disease.
This prestigious award is presented annually to an early career researcher who has made a significant contribution to matrix biology and has excelled in the early stages of their research career.
The award was established following a generous bequest from the estate of Professor John Scott (1931 – 2012) and I am the 4th person to receive this award. As well as giving the John Scott Award Lecture at the BSMB Autumn meeting in Cardiff, the awardee is also invited to write a review on a topic of their choice for publication in International Journal of Experimental Pathology (IJEP).
My talk will be titled “Fibrosis, Cancer and the Pre-Metastatic Niche: Implications for Lysyl Oxidases in Cancer Progression and Metastasis” and will focus on my research into the importance of the Lysyl Oxidase family in cancer.
Early career researchers, up to the age of 36 are encouraged to apply and more information can be found on the BSMB Young Investigator John Scott Award page.
Nominations for the 2017 award will open early next year
BSMB Young Investigator Award: The John Scott Lecture
Thomas R. Cox
University of Copenhagen, Denmark
Fibrosis, Cancer and the Pre-Metastatic Niche:
Implications for Lysyl Oxidases in Cancer Progression and 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.
Over the last 2 decades there has been an increasing number of research papers published investigating the function and role of a family of secreted enzymes called the lysyl oxidases. Lysyl oxidases are not only expressed in animals, but also many other eukaryotes, as well as bacteria and archaea, revealing a pre-metazoan origin for this gene family. Lysyl oxidases are copper-dependent enzymes that oxidize primary amine substrates to reactive aldehydes. The best-studied role of these enzymes is in the post-translational remodelling of the ECM through cross-linking collagens and elastin. To date, a functional role for the lysyl oxidases in cancer has been reported in breast, colorectal, prostate, gastric, and pancreatic cancer, head and neck squamous cell carcinoma, renal clear cell carcinoma, melanoma, oral and oropharyngeal carcinoma, as well as basal and squamous cell skin carcinoma.
My research has focused on how lysyl oxidase (LOX) driven ECM remodeling influences cancer progression, therapy response, and metastatic dissemination in solid tumours. Specifically I have shown that LOX-driven changes in the ECM are critical in modulating Src, FAK and Akt phosphorylation/activation, VEGF-driven angiogenesis, and nFATc1-mediated osteoclastogenesis. Over the years I have shown the importance of aberrant LOX expression and activity in cancer, including the role in ER-negative breast cancer bone metastasis through the generation of pre-metastatic niches; the action of LOX and LOX activity in organ fibrosis, and how this enhances metastatic colonisation of cancer cells in these tissues; and how LOX expression and activity 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, these 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, the targeting of solid tumours with lysyl oxidase inhibitors in the clinic will likely prove a powerful cancer treatment bringing hope to primary and metastatic cancer patients.