Seminar: Biochemical and biomechanical interplay in breast cancer progression
| Dates: | 22 February 2019 |
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| Times: | 13:00 - 14:00 |
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| What is it: | Seminar |
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| Organiser: | Faculty of Biology, Medicine and Health |
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| Who is it for: | University staff, Current University students |
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| Speaker: | Michael Samuel |
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The extra-cellular matrix (ECM) is a source of biochemical and biomechanical influences that direct cell proliferation and fate. However, the molecular mechanisms underlying the interplay between these influences and tissue homeostasis are still relatively ill-defined. The ROCK signalling pathway lies at the interface between mechanical and biochemical signalling. ROCK signalling promotes tumour progression by increasing ECM production, elevating ECM stiffness and enhancing integrin-mediated mechanotransduction signalling in tumours (1,2). We now have new insight into the mechanisms by which breast cancers regulate their ECM by recruiting and educating tumour-promoting fibroblasts in a ROCK-dependent manner by co-opting signalling via the integrated stress response. ROCK-educated fibroblasts are more effective at producing and remodelling the ECM and accelerating tumour progression. Furthermore, mimicking the early mammary cancer environment of enhanced compressive stress rapidly activates the Rho-ROCK pathway in early tumours, revealing a novel mechanism by which ROCK signalling is activated in tumours that are rapidly growing in a confined space. As this pathway in turn regulates the key mechanical properties of the microenvironment, we propose that ROCK promotes cancer progression via a mechano-reciprocal feed-forward mechanism and that inhibiting the secreted effectors of ROCK that regulate the ECM by educating cancer-associated fibroblasts may be a novel therapeutic approach to target cancers. To this end, we have identified and validated in vivo, key targetable proteins secreted by mammary tumour cells following ROCK activation, that are capable of inducing fibroblast recruitment and tumour-promoting ECM remodelling.
1. Samuel et al. Cancer Cell 19:776-91
2. Kular et al. Developmental Cell 35:759-74
Speaker
Michael Samuel
Organisation: Centre for Cancer Biology, University of South Australia
Travel and Contact Information
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Lecture Theatre
Michael Smith Building
Manchester
