ECM remodeling during cancer progression
| Dates: | 26 January 2016 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Life Sciences |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Dr Janine Erler |
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The extracellular matrix (ECM) is one of the most important regulators of cellular and tissue function in the body. The ECM is known to play a critical role in driving cancer progression, and yet we lack knowledge of how ECM is altered during tumour progression to promote cancer metastasis. We have found that an enzyme secreted by tumour and stromal cells called lysyl oxidase (LOX) is responsible for altering the ECM at primary and metastatic sites to greatly enhance metastasis. LOX is an amine oxidase that catalyses the crosslinking of collagens and elastin in the ECM. LOX activity alters the structural and biochemical properties of the ECM, to drive cell proliferation, invasion and angiogenesis. Importantly, LOX modifies pre-metastatic tissue microenvironments prior to tumour cell arrival, enhancing metastatic colonisation and outgrowth. Recently, we showed that hypoxia inactivates cancer-associated fibroblasts to decrease tumour stiffness and metastasis. These effects could be mimicked through inhibition of prolyl hydroxylase domain protein 2 (PHD2), a master regulator of hypoxia-inducible factor 1 alpha (HIF1a). These findings support use of PHD inhibitors in the clinic to prevent cancer progression. Our current research focused on further investigating how the ECM is remodelled during cancer progression and how this impacts on cell behaviour to drive metastasis.
Speaker
Dr Janine Erler
Organisation: University of Copenhagen
Travel and Contact Information
Find event
Michael Smith Lecture Theatre
Michael Smith Building
Manchester
