SOX-2 mediated upregulation of CD24 promotes adaptive resistance towards targeted therapy in melanoma
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ABSTRACT:
PROVIDER: PRJNA416292 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Melanoma is one of the most aggressive types of skin cancer and is often characterized by a constitutively activate RAS-RAF-MEK-ERK pathway. For targeted therapy, BRAF inhibitors are available that are powerful in the beginning but resistance occurs rather fast. A better understanding of the underlying mechanisms of resistance is urgently needed to increase the success of the treatment. Here, we observed that in targeted therapy resistant, melanoma-derived induced pluripotent cancer cells (iPCCs) SOX2 and CD24 are upregulated. It is known that both SOX2 and CD24 expression promote an undifferentiated and cancer stem cell like phenotype, which is associated with higher therapy resistance. We therefore elucidated the role of SOX2 and CD24 in targeted therapy resistance in more detail. We found that SOX2 and CD24 are upregulated upon BRAF inhibitor treatment and that SOX2 is able to upregulate the expression of CD24 by binding to the CD24 promoter. Furthermore, we show that SOX2 or CD24 overexpression significantly increase the resistance towards BRAF inhibitors, while SOX2 knock-down rendered cell sensitive towards treatment. Moreover, CD24 and SOX2 are able to upregulate Src and STAT3 activity which could contribute to the increased resistance. Importantly, CD24 knockdown or Src inhibition in resistant SOX2 overexpressing cells, the sensitivity towards BRAF inhibitors was re-established. Hence, we suggest a novel mechanism of adaptive resistance whereby BRAF inhibition is circumvented via the upregulation of CD24 by SOX2 resulting in increased activity of Scr and STAT3. Thus, to prevent adaptive resistance it might be beneficial to use Src or STAT3 inhibitors together with MAPK pathway inhibitors.
2018-05-15 | GSE106321 | GEO
Project description:Expression profiling of CD24+ and CD24- population cells from myeloma cell lines. Results provide insight into the role of CD24+ cells in myeloma development. Keywords: multiple myeloma, cancer stem cell, CD24
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Project description:Being involved in adhesion, migration, and invasion, the highly glycosylated signal transducer CD24 (cluster of differentiation 24) has been implicated to play an essential role during carcinogenesis. Previously, the molecular and (epi)genetic regulation of CD24 has been characterized in testicular germ cell tumors (GCT). Here, CD24 was exclusively found in embryonal carcinoma (EC), which represents the stem cell like population of GCT (see project PXD025110). For a better understanding of the molecular function of CD24, this study aimed at the identification of the direct interaction partners of CD24 not only in GCTs, but also in other urologic malignancies, such as urothelial- (UC), prostate- (PC), and renal cell carcinoma (RCC). For this purpose, co-immunoprecipitations of CD24 were performed in GCT, UC, PC, and RCC cell lines, while CD24-deficient EC cells as well as IgG2a controls were included for high validity. Extracted proteome was measured by liquid-chromatography coupled with mass spectrometry (LS-MS).
2023-05-10 | PXD039063 | Pride
Project description:CD24, or heat stable antigen, is a cell surface sialoglycoprotein expressed on immature cells that disappears after the cells have reached their final differentiation stage. CD24 may be important in human embryonic kidney epithelial cell differentiation. In mice, CD24 expression is up-regulated in the early metanephros and localized to developing epithelial structures but the role and expression of CD24 in the developing human kidney has not been well described. In normal human fetal kidneys from 8 to 38 weeks gestation, CD24 expression was up-regulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape nephron; however individual CD24+ cells were identified in the interstitium of later gestation and postnatal kidneys. In freshly isolated cells, FACS analysis demonstrated distinct CD24+ and CD24+133+ cell populations, constituting up to 16% and 14% respectively of the total cells analyzed. Isolated and expanded CD24+ clones displayed features of an epithelial progenitor cell line. Early fetal urinary tract obstruction resulted in an upregulation of CD24 expression, both in developing epithelial structures of early gestation kidneys and in the cells of the injured tubular epithelium of the later gestation kidneys. These results highlight the cell specific expression of CD24 in the developing human kidney and dysregulation in fetal urinary tract obstruction. We used microarrays to define the differences in global gene expression between obstructed and normal human fetal kidneys.
2009-11-11 | GSE18969 | GEO
Project description:Expression data from WT CD24+CD172a+ cDC2s, WT CD24–CD172+ cDC2s, and WT CD24+CD172a– cDC1s
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Project description:CD24, or heat stable antigen, is a cell surface sialoglycoprotein expressed on immature cells that disappears after the cells have reached their final differentiation stage. CD24 may be important in human embryonic kidney epithelial cell differentiation. In mice, CD24 expression is up-regulated in the early metanephros and localized to developing epithelial structures but the role and expression of CD24 in the developing human kidney has not been well described. In normal human fetal kidneys from 8 to 38 weeks gestation, CD24 expression was up-regulated and restricted to the early epithelial aggregates of the metanephric blastema and to the committed proliferating tubular epithelia of the S-shape nephron; however individual CD24+ cells were identified in the interstitium of later gestation and postnatal kidneys. In freshly isolated cells, FACS analysis demonstrated distinct CD24+ and CD24+133+ cell populations, constituting up to 16% and 14% respectively of the total cells analyzed. Isolated and expanded CD24+ clones displayed features of an epithelial progenitor cell line. Early fetal urinary tract obstruction resulted in an upregulation of CD24 expression, both in developing epithelial structures of early gestation kidneys and in the cells of the injured tubular epithelium of the later gestation kidneys. These results highlight the cell specific expression of CD24 in the developing human kidney and dysregulation in fetal urinary tract obstruction. We used microarrays to define the differences in global gene expression between obstructed and normal human fetal kidneys. We analyzed RNA extracted from human fetal kidneys between the gestational ages 8 and 18 weeks gestation. This dataset is part of the TransQST collection.
2009-11-11 | E-GEOD-18969 | biostudies-arrayexpress
Project description:Gene expression were identified with or without CD24 gene silencing in Du145 cells. RNA isolated from 5 independent cultures of Scramble control, 3 cultures of CD24-ShRNA1 and 2 cultures of CD24-ShRNA2 were tested using Affimatrx Human U133 Plus 2.0 microarrays.
2014-05-05 | E-GEOD-46708 | biostudies-arrayexpress
Project description:Introduction: In vitro 3-dimension spheroid culture has been widely used as model to enrich CD44+CD24dim/- cancer stem cells with high ALDH1 activity. However, present of the CD24+ population in the 3D spheroid also requests further attention as this side-population of cells may response differently to drug treatment comparing to the cancer stem cells. Methods: In this study, CD24+ population from the MCF-7 spheroid was sorted and subjected to spheroid formation test, stem cell markers immunofluorescence, invasion/migration test, and microRNA expression profiling. MCF-7 CD24+ cells sorted from primary spheroid reform 3D spheroid after longer period of time associated with dim expression of surface SOX-2, CD44, CD49f and Nanog comparing to the primary spheroid. Results: Remarkably, the MCF-7 CD24+ cells was found with high expression of ALDH1 protein, which subsequently contributed to higher resistant against doxorubicin and cisplatin. MicroRNA profiling has shown that absent of cancer stem cell phenotypes were contributed by the downregulation of major cancer stem cells related pathways including Hedgehog, Wnt and MAPK signalling pathways. Besides, resistance of CD24+ cells was correlated to dyregulation of cell death pathway.
2018-03-12 | GSE95598 | GEO
Project description:This study is aimed to evaluate the performance of the Micromedic CD24 assay in identifying colorectal adenoma using Western blot and ELISA assays. These assays are designed to detect CD24 protein in peripheral blood leukocytes (PBL). Elevated levels of CD24 may be indicative of colorectal adenoma (inclusive of optically detectable early adenoma to late adenoma, and cancer).
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