Matches in SemOpenAlex for { <https://semopenalex.org/work/W2569451019> ?p ?o ?g. }
- W2569451019 abstract "Melanoma is a highly metastatic type of cancer that is resistant to all standard anticancer therapies and thus has a poor prognosis. Therefore, metastatic melanoma represents a significant clinical problem and requires novel and effective targeted therapies. The protein kinase C (PKC) family comprises multiple isoforms of serine/threonine kinases that possess distinct roles in cancer development and progression. In this study, we determined whether inhibition of PKC could revert a major process required for melanoma progression and metastasis; i.e. the E- to N-cadherin switch. The cadherin switch was analyzed in different patient-derived primary tumors and their respective metastatic melanoma cells to determine the appropriate cellular model (aggressive E-cadherin-negative/N-cadherin-positive metastasis-derived melanoma cells). Next, PKC inhibition in two selected metastatic melanoma cell lines, was performed by using either pharmacological inhibitors (Gö6976 and Gö6983) or stable lentiviral shRNA transduction. The expression of E-cadherin and N-cadherin was determined by western blot. The consequences of cadherin switch reversion were analyzed: cell morphology, intercellular interactions, and β-catenin subcellular localization were analyzed by immunofluorescence labeling and confocal microscopy; cyclin D1 expression was analyzed by western blot; cell metastatic potential was determined by anchorage-independent growth assay using methylcellulose as semi-solid medium and cell migration potential by wound healing and transwell assays. Gö6976 but not Gö6983 reversed the E- to N-cadherin switch and as a consequence induced intercellular interactions, profound morphological changes from elongated mesenchymal-like to cuboidal epithelial-like shape, β-catenin translocation from the nucleus to the plasma membrane inhibiting its oncogenic function, and reverting the metastatic potential of the aggressive melanoma cells. Comparison of the target spectrum of these inhibitors indicated that these observations were not the consequence of the inhibition of conventional PKCs (cPKCs), but allowed the identification of a novel serine/threonine kinase, i.e. protein kinase Cμ, also known as protein kinase D1 (PKD1), whose specific inhibition allows the reversion of the metastatic phenotype in aggressive melanoma. In conclusion, our study suggests, for the first time, that while cPKCs don’t embody a pertinent therapeutic target, inhibition of PKD1 represents a novel attractive approach for the treatment of metastatic melanoma." @default.
- W2569451019 created "2017-01-13" @default.
- W2569451019 creator A5016620432 @default.
- W2569451019 creator A5017477419 @default.
- W2569451019 creator A5029044608 @default.
- W2569451019 creator A5065031717 @default.
- W2569451019 creator A5074573688 @default.
- W2569451019 creator A5087159704 @default.
- W2569451019 date "2017-01-05" @default.
- W2569451019 modified "2023-09-24" @default.
- W2569451019 title "Protein kinase C inhibitor Gö6976 but not Gö6983 induces the reversion of E- to N-cadherin switch and metastatic phenotype in melanoma: identification of the role of protein kinase D1" @default.
- W2569451019 cites W1435076864 @default.
- W2569451019 cites W1500657758 @default.
- W2569451019 cites W1573000660 @default.
- W2569451019 cites W1641731911 @default.
- W2569451019 cites W176465638 @default.
- W2569451019 cites W1889806365 @default.
- W2569451019 cites W1902144921 @default.
- W2569451019 cites W1963877296 @default.
- W2569451019 cites W1963892864 @default.
- W2569451019 cites W1964505996 @default.
- W2569451019 cites W1967009719 @default.
- W2569451019 cites W1976205102 @default.
- W2569451019 cites W1976546353 @default.
- W2569451019 cites W1981957327 @default.
- W2569451019 cites W1984264347 @default.
- W2569451019 cites W1985688210 @default.
- W2569451019 cites W1992094591 @default.
- W2569451019 cites W1992706018 @default.
- W2569451019 cites W1998349282 @default.
- W2569451019 cites W2000271974 @default.
- W2569451019 cites W2001179486 @default.
- W2569451019 cites W2002041258 @default.
- W2569451019 cites W2002760530 @default.
- W2569451019 cites W2002893170 @default.
- W2569451019 cites W2005339886 @default.
- W2569451019 cites W2007500163 @default.
- W2569451019 cites W2012670804 @default.
- W2569451019 cites W2018884883 @default.
- W2569451019 cites W2021306647 @default.
- W2569451019 cites W2030090912 @default.
- W2569451019 cites W2033498252 @default.
- W2569451019 cites W2033744588 @default.
- W2569451019 cites W2041797033 @default.
- W2569451019 cites W2044653832 @default.
- W2569451019 cites W2045471555 @default.
- W2569451019 cites W2054531472 @default.
- W2569451019 cites W2055464156 @default.
- W2569451019 cites W2058434027 @default.
- W2569451019 cites W2064949856 @default.
- W2569451019 cites W2065136679 @default.
- W2569451019 cites W2065832539 @default.
- W2569451019 cites W2066717393 @default.
- W2569451019 cites W2067828467 @default.
- W2569451019 cites W2075225790 @default.
- W2569451019 cites W2076583198 @default.
- W2569451019 cites W2077462602 @default.
- W2569451019 cites W2078216136 @default.
- W2569451019 cites W2080149190 @default.
- W2569451019 cites W2080558800 @default.
- W2569451019 cites W2081527131 @default.
- W2569451019 cites W2081939461 @default.
- W2569451019 cites W2082905439 @default.
- W2569451019 cites W2088192465 @default.
- W2569451019 cites W2089342379 @default.
- W2569451019 cites W2089475281 @default.
- W2569451019 cites W2097928320 @default.
- W2569451019 cites W2098820114 @default.
- W2569451019 cites W2111089430 @default.
- W2569451019 cites W2117933964 @default.
- W2569451019 cites W2118252933 @default.
- W2569451019 cites W2124557759 @default.
- W2569451019 cites W2127190481 @default.
- W2569451019 cites W2129775855 @default.
- W2569451019 cites W2137530154 @default.
- W2569451019 cites W2139834804 @default.
- W2569451019 cites W2143759076 @default.
- W2569451019 cites W2146654096 @default.
- W2569451019 cites W2149860077 @default.
- W2569451019 cites W2165901622 @default.
- W2569451019 cites W2314140400 @default.
- W2569451019 cites W2338443866 @default.
- W2569451019 cites W2428747277 @default.
- W2569451019 cites W4211224216 @default.
- W2569451019 cites W4241605155 @default.
- W2569451019 cites W4244068819 @default.
- W2569451019 cites W649916569 @default.
- W2569451019 doi "https://doi.org/10.1186/s12885-016-3007-5" @default.
- W2569451019 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5217271" @default.
- W2569451019 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28056869" @default.
- W2569451019 hasPublicationYear "2017" @default.
- W2569451019 type Work @default.
- W2569451019 sameAs 2569451019 @default.
- W2569451019 citedByCount "14" @default.
- W2569451019 countsByYear W25694510192018 @default.
- W2569451019 countsByYear W25694510192019 @default.
- W2569451019 countsByYear W25694510192020 @default.
- W2569451019 countsByYear W25694510192021 @default.
- W2569451019 countsByYear W25694510192022 @default.
- W2569451019 countsByYear W25694510192023 @default.