Matches in SemOpenAlex for { <https://semopenalex.org/work/W3130190746> ?p ?o ?g. }
- W3130190746 abstract "ABSTRACT The tumor stroma and its cellular components are known to play an important role in tumor resilience towards treatment. Here, we report a novel resistance mechanism in melanoma that is elicited by BRAF inhibitors (BRAFi)-induced non-canonical nuclear β-catenin signaling in cancer-associated fibroblasts (CAFs). Our study reveals that BRAFi leads to an expanded CAF population with increased β-catenin nuclear accumulation and enhances their biological properties. This CAF subpopulation is essential for melanoma cells to grow and resist to BRAFi/MEK inhibitors (MEKi). Mechanistically, BRAFi induces BRAF and CRAF dimerization and subsequently the activation of ERK signaling in CAFs, leading to the inactivation of the β-catenin destruction complex. By RNA-Seq, periostin (POSTN) is identified as a major downstream effector of β catenin in CAFs and can compensate for the loss of β-catenin in CAFs in conferring melanoma cell BRAFi/MEKi resistance. Moreover, POSTN reactivates the ERK pathway, which is inhibited by BRAFi/MEKi, in melanoma cells through PI3K/AKT signaling. Our data underscore the roles of BRAFi-induced CAF reprogramming in matrix remodeling and therapeutic escape of melanoma cells and reveal POSTN as an important matrix target to eliminate BRAFi/MEKi resistance in melanoma." @default.
- W3130190746 created "2021-03-01" @default.
- W3130190746 creator A5013343878 @default.
- W3130190746 creator A5066807605 @default.
- W3130190746 creator A5070085914 @default.
- W3130190746 creator A5084148508 @default.
- W3130190746 creator A5088666930 @default.
- W3130190746 date "2021-02-18" @default.
- W3130190746 modified "2023-10-16" @default.
- W3130190746 title "BRAF inhibitors reprogram cancer-associated fibroblasts to drive matrix remodeling and therapeutic escape in melanoma" @default.
- W3130190746 cites W1529396499 @default.
- W3130190746 cites W1957521115 @default.
- W3130190746 cites W1971750711 @default.
- W3130190746 cites W1977889509 @default.
- W3130190746 cites W1982078590 @default.
- W3130190746 cites W1984769051 @default.
- W3130190746 cites W1985309852 @default.
- W3130190746 cites W1988329060 @default.
- W3130190746 cites W2004191314 @default.
- W3130190746 cites W2004295816 @default.
- W3130190746 cites W2006419043 @default.
- W3130190746 cites W2006631235 @default.
- W3130190746 cites W2017695960 @default.
- W3130190746 cites W2023046293 @default.
- W3130190746 cites W2031882612 @default.
- W3130190746 cites W2031903272 @default.
- W3130190746 cites W2034792192 @default.
- W3130190746 cites W2043691868 @default.
- W3130190746 cites W2051165598 @default.
- W3130190746 cites W2061339803 @default.
- W3130190746 cites W2067400935 @default.
- W3130190746 cites W2075363163 @default.
- W3130190746 cites W2079019573 @default.
- W3130190746 cites W2084929197 @default.
- W3130190746 cites W2086859574 @default.
- W3130190746 cites W2089704546 @default.
- W3130190746 cites W2089956125 @default.
- W3130190746 cites W2095852623 @default.
- W3130190746 cites W2102512718 @default.
- W3130190746 cites W2102531423 @default.
- W3130190746 cites W2116102471 @default.
- W3130190746 cites W2116315632 @default.
- W3130190746 cites W2122428292 @default.
- W3130190746 cites W2122914905 @default.
- W3130190746 cites W2124342021 @default.
- W3130190746 cites W2126731289 @default.
- W3130190746 cites W2139007645 @default.
- W3130190746 cites W2144300167 @default.
- W3130190746 cites W2144325011 @default.
- W3130190746 cites W2144403534 @default.
- W3130190746 cites W2144796426 @default.
- W3130190746 cites W2147799284 @default.
- W3130190746 cites W2149662085 @default.
- W3130190746 cites W2155381255 @default.
- W3130190746 cites W2157450847 @default.
- W3130190746 cites W2158217645 @default.
- W3130190746 cites W2160378889 @default.
- W3130190746 cites W2167859307 @default.
- W3130190746 cites W2168249402 @default.
- W3130190746 cites W2400442973 @default.
- W3130190746 cites W2429316017 @default.
- W3130190746 cites W2516629192 @default.
- W3130190746 cites W2586528843 @default.
- W3130190746 cites W2587816384 @default.
- W3130190746 cites W2590390825 @default.
- W3130190746 cites W2736470274 @default.
- W3130190746 cites W2746601664 @default.
- W3130190746 cites W2767156586 @default.
- W3130190746 cites W2789715646 @default.
- W3130190746 cites W2815877626 @default.
- W3130190746 cites W2907352888 @default.
- W3130190746 cites W2911883556 @default.
- W3130190746 cites W2919453888 @default.
- W3130190746 cites W2938062190 @default.
- W3130190746 cites W2938280489 @default.
- W3130190746 cites W2943253686 @default.
- W3130190746 cites W2943366514 @default.
- W3130190746 cites W2951222857 @default.
- W3130190746 cites W2963168634 @default.
- W3130190746 cites W2990985157 @default.
- W3130190746 cites W2995270736 @default.
- W3130190746 cites W2999893607 @default.
- W3130190746 cites W3003058300 @default.
- W3130190746 cites W4234665826 @default.
- W3130190746 cites W4249273120 @default.
- W3130190746 cites W561543316 @default.
- W3130190746 cites W969758129 @default.
- W3130190746 doi "https://doi.org/10.1101/2021.02.18.431841" @default.
- W3130190746 hasPublicationYear "2021" @default.
- W3130190746 type Work @default.
- W3130190746 sameAs 3130190746 @default.
- W3130190746 citedByCount "0" @default.
- W3130190746 crossrefType "posted-content" @default.
- W3130190746 hasAuthorship W3130190746A5013343878 @default.
- W3130190746 hasAuthorship W3130190746A5066807605 @default.
- W3130190746 hasAuthorship W3130190746A5070085914 @default.
- W3130190746 hasAuthorship W3130190746A5084148508 @default.
- W3130190746 hasAuthorship W3130190746A5088666930 @default.
- W3130190746 hasBestOaLocation W31301907461 @default.
- W3130190746 hasConcept C121608353 @default.