BEGIN:VCALENDAR
PRODID:-//Columba Systems Ltd//NONSGML CPNG/SpringViewer/ICal Output/3.3-
 M3//EN
VERSION:2.0
CALSCALE:GREGORIAN
METHOD:PUBLISH
BEGIN:VEVENT
DTSTAMP:20190205T104502Z
DTSTART:20190222T130000Z
DTEND:20190222T140000Z
SUMMARY:Seminar: Biochemical and biomechanical interplay in breast cancer
  progression
UID:{http://www.columbasystems.com/customers/uom/gpp/eventid/}suq-jrrmyb9
 a-oggzj
DESCRIPTION:The extra-cellular matrix (ECM) is a source of biochemical an
 d biomechanical influences that direct cell proliferation and fate. Howe
 ver\, the molecular mechanisms underlying the interplay between these in
 fluences and tissue homeostasis are still relatively ill-defined. The RO
 CK signalling pathway lies at the interface between mechanical and bioch
 emical signalling. ROCK signalling promotes tumour progression by increa
 sing ECM production\, elevating ECM stiffness and enhancing integrin-med
 iated mechanotransduction signalling in tumours (1\,2). We now have new 
 insight into the mechanisms by which breast cancers regulate their ECM b
 y recruiting and educating tumour-promoting fibroblasts in a ROCK-depend
 ent manner by co-opting signalling via the integrated stress response. R
 OCK-educated fibroblasts are more effective at producing and remodelling
  the ECM and accelerating tumour progression. Furthermore\, mimicking th
 e early mammary cancer environment of enhanced compressive stress rapidl
 y activates the Rho-ROCK pathway in early tumours\, revealing a novel me
 chanism by which ROCK signalling is activated in tumours that are rapidl
 y growing in a confined space. As this pathway in turn regulates the key
  mechanical properties of the microenvironment\, we propose that ROCK pr
 omotes cancer progression via a mechano-reciprocal feed-forward mechanis
 m and that inhibiting the secreted effectors of ROCK that regulate the E
 CM by educating cancer-associated fibroblasts may be a novel therapeutic
  approach to target cancers. To this end\, we have identified and valida
 ted in vivo\, key targetable proteins secreted by mammary tumour cells f
 ollowing ROCK activation\, that are capable of inducing fibroblast recru
 itment and tumour-promoting ECM remodelling.\n \n1. Samuel et al. Cancer
  Cell 19:776-91\n2. Kular et al. Developmental Cell 35:759-74
STATUS:TENTATIVE
TRANSP:TRANSPARENT
CLASS:PUBLIC
LOCATION:Lecture Theatre\, Michael Smith Building\, Manchester
END:VEVENT
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