Matches in SemOpenAlex for { <https://semopenalex.org/work/W1726565541> ?p ?o ?g. }
Showing items 1 to 96 of
96
with 100 items per page.
- W1726565541 abstract "Breast cancer is the most common form of cancer in women. While the prognosis for breast cancer patients without local or distal dissemination is relatively favorable, the prognosis is considerably worse once distal metastasis has been established. It is therefore imperative to identify molecular targets and develop novel anti-metastatic therapies that will stop, reduce or delay the spread and growth of breast cancer metastasis. Low expression of Wnt-5a in a primary breast tumor is associated with shorter recurrence free survival, suggesting that Wnt-5a acts to restrict breast cancer metastasis. Moreover, Wnt-5a is known to inhibit migration of breast epithelial cells in culture and expression of Wnt-5a potentiates activation of the receptor tyrosine kinase DDR1, a collagen receptor implicated in cell adhesion and migration. This thesis describes the identification of DARPP-32 as a novel interactionpartner to DDR1. We demonstrate that DARPP-32 inhibits MCF-7 cell migration and that this effect requires phosphorylation of threonine-34, an event catalyzed by protein kinase A (PKA) and strongly induced by detachment of cells from the culture substrate. DARPP-32 mediated inhibition of migration proved to be dependent on DDR1 expression consolidating a functional relevance of the interaction between DARPP-32 and DDR1. In addition, we found that Wnt-5a could directly trigger a cAMP response that resulted in phosphorylation of DARPP-32 and stimulation with Wnt-5a was nessecary for DARPP-32 mediated inhibition of cell migration in wound healing assay. The anti-migratory effects of Wnt-5a and DARPP-32 were reduced by dominant negative CREB, which suggests that CREB plays a functional role in this signalling mechanism. Finally, we found that phospho-DARPP-32 inhibited the activity of the focal adhesion kinase (FAK) in MCF-7 breast cancer cells, and that MCF-7 cells expressing phospho-DARPP-32 displayed less filopodia formation. These results suggest that DARPP-32 restricts the migration of breast epithelial cells via both a transcription dependent mechanism that involves CREB and a transcription independent mechanism affecting FAK. Pharmacological activation of this pathway may constitute a novel way of limiting breast cancer metastasis. (Less)" @default.
- W1726565541 created "2016-06-24" @default.
- W1726565541 creator A5005601279 @default.
- W1726565541 date "2008-01-01" @default.
- W1726565541 modified "2023-09-28" @default.
- W1726565541 title "Role of DARPP-32 in Breast Cancer Cell Signalling and Migration" @default.
- W1726565541 cites W1500907336 @default.
- W1726565541 cites W1969345980 @default.
- W1726565541 cites W1970290214 @default.
- W1726565541 cites W1985643173 @default.
- W1726565541 cites W1985990006 @default.
- W1726565541 cites W1995140110 @default.
- W1726565541 cites W2017079446 @default.
- W1726565541 cites W2023186669 @default.
- W1726565541 cites W2030030102 @default.
- W1726565541 cites W2048209624 @default.
- W1726565541 cites W2054649179 @default.
- W1726565541 cites W2061821798 @default.
- W1726565541 cites W2083630984 @default.
- W1726565541 cites W2093784914 @default.
- W1726565541 cites W2106837751 @default.
- W1726565541 cites W2116566070 @default.
- W1726565541 cites W2139110700 @default.
- W1726565541 cites W2141030634 @default.
- W1726565541 cites W2142127733 @default.
- W1726565541 cites W2155348369 @default.
- W1726565541 cites W2155959312 @default.
- W1726565541 cites W2165786593 @default.
- W1726565541 cites W2168181903 @default.
- W1726565541 cites W2187913346 @default.
- W1726565541 cites W2411291005 @default.
- W1726565541 hasPublicationYear "2008" @default.
- W1726565541 type Work @default.
- W1726565541 sameAs 1726565541 @default.
- W1726565541 citedByCount "0" @default.
- W1726565541 crossrefType "dissertation" @default.
- W1726565541 hasAuthorship W1726565541A5005601279 @default.
- W1726565541 hasConcept C101544691 @default.
- W1726565541 hasConcept C11960822 @default.
- W1726565541 hasConcept C121608353 @default.
- W1726565541 hasConcept C126322002 @default.
- W1726565541 hasConcept C137620995 @default.
- W1726565541 hasConcept C137738243 @default.
- W1726565541 hasConcept C1491633281 @default.
- W1726565541 hasConcept C185592680 @default.
- W1726565541 hasConcept C2779013556 @default.
- W1726565541 hasConcept C502942594 @default.
- W1726565541 hasConcept C530470458 @default.
- W1726565541 hasConcept C55493867 @default.
- W1726565541 hasConcept C62478195 @default.
- W1726565541 hasConcept C71924100 @default.
- W1726565541 hasConcept C86803240 @default.
- W1726565541 hasConcept C95444343 @default.
- W1726565541 hasConceptScore W1726565541C101544691 @default.
- W1726565541 hasConceptScore W1726565541C11960822 @default.
- W1726565541 hasConceptScore W1726565541C121608353 @default.
- W1726565541 hasConceptScore W1726565541C126322002 @default.
- W1726565541 hasConceptScore W1726565541C137620995 @default.
- W1726565541 hasConceptScore W1726565541C137738243 @default.
- W1726565541 hasConceptScore W1726565541C1491633281 @default.
- W1726565541 hasConceptScore W1726565541C185592680 @default.
- W1726565541 hasConceptScore W1726565541C2779013556 @default.
- W1726565541 hasConceptScore W1726565541C502942594 @default.
- W1726565541 hasConceptScore W1726565541C530470458 @default.
- W1726565541 hasConceptScore W1726565541C55493867 @default.
- W1726565541 hasConceptScore W1726565541C62478195 @default.
- W1726565541 hasConceptScore W1726565541C71924100 @default.
- W1726565541 hasConceptScore W1726565541C86803240 @default.
- W1726565541 hasConceptScore W1726565541C95444343 @default.
- W1726565541 hasLocation W17265655411 @default.
- W1726565541 hasOpenAccess W1726565541 @default.
- W1726565541 hasPrimaryLocation W17265655411 @default.
- W1726565541 hasRelatedWork W1971653872 @default.
- W1726565541 hasRelatedWork W2003049181 @default.
- W1726565541 hasRelatedWork W2037535929 @default.
- W1726565541 hasRelatedWork W2069225985 @default.
- W1726565541 hasRelatedWork W2077282333 @default.
- W1726565541 hasRelatedWork W2080804646 @default.
- W1726565541 hasRelatedWork W2105592383 @default.
- W1726565541 hasRelatedWork W2130671494 @default.
- W1726565541 hasRelatedWork W2142127733 @default.
- W1726565541 hasRelatedWork W2142837526 @default.
- W1726565541 hasRelatedWork W2154450305 @default.
- W1726565541 hasRelatedWork W2157194785 @default.
- W1726565541 hasRelatedWork W2274026040 @default.
- W1726565541 hasRelatedWork W2765894460 @default.
- W1726565541 hasRelatedWork W2770256858 @default.
- W1726565541 hasRelatedWork W2800924700 @default.
- W1726565541 hasRelatedWork W3081893952 @default.
- W1726565541 hasRelatedWork W3174469818 @default.
- W1726565541 hasRelatedWork W3176743338 @default.
- W1726565541 hasRelatedWork W327843650 @default.
- W1726565541 isParatext "false" @default.
- W1726565541 isRetracted "false" @default.
- W1726565541 magId "1726565541" @default.
- W1726565541 workType "dissertation" @default.