Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379184980> ?p ?o ?g. }
- W4379184980 endingPage "9684" @default.
- W4379184980 startingPage "9684" @default.
- W4379184980 abstract "The management of advanced-stage melanoma is clinically challenging, mainly because of its resistance to the currently available therapies. Therefore, it is important to develop alternative therapeutic strategies. The sigma-2 receptor (S2R) is overexpressed in proliferating tumor cells and represents a promising vulnerability to target. Indeed, we have recently identified a potent S2R modulator (BS148) that is effective in melanoma. To elucidate its mechanism of action, we designed and synthesized a BS148 fluorescent probe that enters SK-MEL-2 melanoma cells as assessed using confocal microscopy analysis. We show that S2R knockdown significantly reduces the anti-proliferative effect induced by BS148 administration, indicating the engagement of S2R in BS148-mediated cytotoxicity. Interestingly, BS148 treatment showed similar molecular effects to S2R RNA interference-mediated knockdown. We demonstrate that BS148 administration activates the endoplasmic reticulum stress response through the upregulation of protein kinase R-like ER kinase (PERK), activating transcription factor 4 (ATF4) genes, and C/EBP homologous protein (CHOP). Furthermore, we show that BS148 treatment downregulates genes related to the cholesterol pathway and activates the MAPK signaling pathway. Finally, we translate our results into patient-derived xenograft (PDX) cells, proving that BS148 treatment reduces melanoma cell viability and migration. These results demonstrate that BS148 is able to inhibit metastatic melanoma cell proliferation and migration through its interaction with the S2R and confirm its role as a promising target to treat cancer." @default.
- W4379184980 created "2023-06-03" @default.
- W4379184980 creator A5010179729 @default.
- W4379184980 creator A5017789323 @default.
- W4379184980 creator A5020172375 @default.
- W4379184980 creator A5025848306 @default.
- W4379184980 creator A5028673758 @default.
- W4379184980 creator A5032280206 @default.
- W4379184980 creator A5032700976 @default.
- W4379184980 creator A5035279609 @default.
- W4379184980 creator A5064497021 @default.
- W4379184980 creator A5065030330 @default.
- W4379184980 creator A5068179321 @default.
- W4379184980 creator A5069678973 @default.
- W4379184980 creator A5077228484 @default.
- W4379184980 creator A5077865101 @default.
- W4379184980 creator A5079365060 @default.
- W4379184980 date "2023-06-02" @default.
- W4379184980 modified "2023-09-27" @default.
- W4379184980 title "BS148 Reduces the Aggressiveness of Metastatic Melanoma via Sigma-2 Receptor Targeting" @default.
- W4379184980 cites W1874144828 @default.
- W4379184980 cites W1938480220 @default.
- W4379184980 cites W1951533674 @default.
- W4379184980 cites W1965857762 @default.
- W4379184980 cites W1994224293 @default.
- W4379184980 cites W2000999850 @default.
- W4379184980 cites W2029667189 @default.
- W4379184980 cites W2032510107 @default.
- W4379184980 cites W2033455310 @default.
- W4379184980 cites W2042334642 @default.
- W4379184980 cites W2052273830 @default.
- W4379184980 cites W2060972405 @default.
- W4379184980 cites W2077445354 @default.
- W4379184980 cites W2085933321 @default.
- W4379184980 cites W2087815516 @default.
- W4379184980 cites W2089351812 @default.
- W4379184980 cites W2097775366 @default.
- W4379184980 cites W2098890598 @default.
- W4379184980 cites W2105668062 @default.
- W4379184980 cites W2122387572 @default.
- W4379184980 cites W2131087015 @default.
- W4379184980 cites W2144378472 @default.
- W4379184980 cites W2164674363 @default.
- W4379184980 cites W2171268876 @default.
- W4379184980 cites W2271796329 @default.
- W4379184980 cites W2314811232 @default.
- W4379184980 cites W2318531023 @default.
- W4379184980 cites W2341902059 @default.
- W4379184980 cites W2351409154 @default.
- W4379184980 cites W2413303152 @default.
- W4379184980 cites W2421368074 @default.
- W4379184980 cites W2607129810 @default.
- W4379184980 cites W2618221287 @default.
- W4379184980 cites W2738387201 @default.
- W4379184980 cites W2760281132 @default.
- W4379184980 cites W2890021538 @default.
- W4379184980 cites W2901780362 @default.
- W4379184980 cites W2903880522 @default.
- W4379184980 cites W2904016386 @default.
- W4379184980 cites W2904029294 @default.
- W4379184980 cites W2911724432 @default.
- W4379184980 cites W2938224234 @default.
- W4379184980 cites W2963269355 @default.
- W4379184980 cites W2972008566 @default.
- W4379184980 cites W2980641934 @default.
- W4379184980 cites W2981883000 @default.
- W4379184980 cites W2995339529 @default.
- W4379184980 cites W3025131477 @default.
- W4379184980 cites W3030716880 @default.
- W4379184980 cites W3039627570 @default.
- W4379184980 cites W3091994645 @default.
- W4379184980 cites W3097999154 @default.
- W4379184980 cites W3098082001 @default.
- W4379184980 cites W3098658080 @default.
- W4379184980 cites W3109786692 @default.
- W4379184980 cites W3112981431 @default.
- W4379184980 cites W3118853432 @default.
- W4379184980 cites W3119075839 @default.
- W4379184980 cites W3121181953 @default.
- W4379184980 cites W3164253088 @default.
- W4379184980 cites W3169559834 @default.
- W4379184980 cites W3201798148 @default.
- W4379184980 cites W3208501924 @default.
- W4379184980 cites W3212363098 @default.
- W4379184980 cites W4200289210 @default.
- W4379184980 cites W4206646303 @default.
- W4379184980 cites W4220856798 @default.
- W4379184980 cites W4225808318 @default.
- W4379184980 cites W4313119071 @default.
- W4379184980 cites W4313260641 @default.
- W4379184980 cites W4318194827 @default.
- W4379184980 doi "https://doi.org/10.3390/ijms24119684" @default.
- W4379184980 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37298633" @default.
- W4379184980 hasPublicationYear "2023" @default.
- W4379184980 type Work @default.
- W4379184980 citedByCount "0" @default.
- W4379184980 crossrefType "journal-article" @default.
- W4379184980 hasAuthorship W4379184980A5010179729 @default.