BACKGROUND: Cluster of differentiation 24 (CD24) is a highly glycosylated glycosylphosphatidylinositol (GPI)-anchored surface protein, expressed in various tumor cells, as a \"don\'t eat me\" signaling molecule in tumor immune. This study aimed to investigate the potential features of CD24 in pan-cancer.
METHODS: The correlations between 22 immune cells and CD24 expression were using TIMER analysis. R package \"ESTIMATE\" was used to predict the proportion of immune and stromal cells in pan-cancer. Spearman\'s correlation analysis was performed to evaluate the relationships between CD24 expression and immune checkpoints, chemokines, mismatch repair, tumor mutation burden and microsatellite instability, and qPCR and western blot were conducted to assess CD24 expression levels in liver hepatocellular carcinoma (LIHC). In addition, loss of function was performed for the biological evaluation of CD24 in LIHC.
RESULTS: CD24 expression was positively correlated with myeloid cells, including neutrophils and myeloid-derived suppressor cells, in various tumors, such as BLCA, HNSC-HPV, HNSC, KICH, KIRC, KIRP, TGCT, THCA, THYM, and UCEC. In contrast, anti-tumor NK cells and NKT cells showed a negative association with CD24 expression in BRCA-Her2, ESCA, HNSC-HPV, KIRC, THCA, and THYM. The top three tumors with the highest correlation between CD24 and ImmuneScore were TGCT, THCA, and SKCM. Functional enrichment analysis revealed CD24 expression was negatively associated with various immune-related pathways. Immune checkpoints and chemokines also exhibited inverse correlations with CD24 in CESC, CHOL, COAD, ESCA, READ, TGCT, and THCA. Additionally, CD24 was overexpressed in most tumors, with high CD24 expression in BRCA, LIHC, and CESC correlating with poor prognosis. The TIDE database indicated tumors with high CD24 expression, particularly melanoma, were less responsive to PD1/PD-L1 immunotherapy. Finally, CD24 knockdown resulted in impaired proliferation and cell cycle progression in LIHC.
CONCLUSIONS: CD24 participates in regulation of immune infiltration, influences patient prognosis and serves as a potential tumor marker.

BACKGROUND: Basal cells (BCs) are bronchial progenitor/stem cells that can regenerate injured airway that, in smokers, may undergo malignant transformation. As a model for early stages of lung carcinogenesis, we set out to characterize cytologically normal BC outgrowths from never-smokers and ever-smokers without cancers (controls), as well as from the normal epithelial \"field\" of ever-smokers with anatomically remote cancers, including lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) (cases).
METHODS: Primary BCs were cultured and expanded from endobronchial brushings taken remote from the site of clinical or visible lesions/tumors. Donor subgroups were tested for growth, morphology, and underlying molecular features by qRT-PCR, RNAseq, flow cytometry, immunofluorescence, and immunoblot.
RESULTS: (a) the BC population includes epithelial cell adhesion molecule (EpCAM) positive and negative cell subsets; (b) smoking reduced overall BC proliferation corresponding with a 2.6-fold reduction in the EpCAMpos/ITGA6 pos/CD24pos stem cell fraction; (c) LUSC donor cells demonstrated up to 2.8-fold increase in dysmorphic BCs; and (d) cells procured from LUAD patients displayed increased proliferation and S-phase cell cycle fractions. These differences corresponded with: (i) disparate NOTCH1/NOTCH2 transcript expression and altered expression of potential downstream (ii) E-cadherin (CDH1), tumor protein-63 (TP63), secretoglobin family 1a member 1 (SCGB1A1), and Hairy/enhancer-of-split related with YRPW motif 1 (HEY1); and (iii) reduced EPCAM and increased NK2 homeobox-1 (NKX2-1) mRNA expression in LUAD donor BCs.
CONCLUSIONS: These and other findings demonstrate impacts of donor age, smoking, and lung cancer case-control status on BC phenotypic and molecular traits and may suggest Notch signaling pathway deregulation during early human lung cancer pathogenesis.

Anastasis is a phenomenon observed in cancer cells, where cells that have initiated apoptosis are able to recover and survive. This molecular event is increasingly recognized as a potential contributor to cancer metastasis, facilitating the survival and migration of tumor cells. Nevertheless, the identification of a specific surface marker for detecting cancer cells in anastasis remained elusive. Here we report our observation that the cell surface expression of CD24 is preferentially enriched in a non-adherent FSClowSSChigh melanoma subpopulation, which is generally considered a non-viable population in cultivated melanoma cell lines. More than 90% of non-adherent FSClowSSChighCD24+ve metastatic melanoma cells exhibited bonafide features of apoptosis on the cell surface and in the nucleus, marking apoptotic or seemingly apoptotic subpopulations of the in vitro cultivated metastatic melanoma cell lines. Unexpectedly, however, the CD24+ve subpopulation, despite being apoptotic, showed evidence of metabolic activity and exhibited proliferative capacities, including anchorage-independent growth, when inoculated in soft agarose growth medium. These findings indicate that apoptotic FSClowSSChighCD24+ve melanoma subpopulations are capable of reversing the progression of apoptosis. We report CD24 as the first novel cell surface marker for anastasis in melanoma cells.

Cancer immunotherapy has revolutionized the treatment landscape by harnessing the power of the immune system to combat malignancies. Two of the most promising players in this field are cluster of differentiation 24 (CD24) and sialic acid-binding Ig-like lectin 10 (Siglec-10), and both of them play pivotal roles in modulating immune responses. CD24, a cell surface glycoprotein, emerges as a convincing fundamental signal transducer for therapeutic intervention, given its significant implication in the processes related to tumour progression and immunogenic evasion. Additionally, the immunomodulatory functions of Siglec-10, a prominent member within the Siglec family of immune receptors, have recently become a crucial point of interest, particularly in the context of the tumour microenvironment. Hence, the intricate interplay of both CD24 and Siglec-10 assumes a critical role in fostering tumour growth, facilitating metastasis and also orchestrating immune evasion. Recent studies have found multiple evidences supporting the therapeutic potential of targeting CD24 in cancer treatment. Siglec-10, on the other hand, exhibits immunosuppressive properties that contribute to immune tolerance within the tumour microenvironment. Therefore, we delve into the complex mechanisms through which Siglec-10 modulates immune responses and facilitates immune escape in cancer. Siglec-10 also acts as a viable target for cancer immunotherapy and presents novel avenues for the development of therapeutic interventions. Furthermore, we examine the synergy between CD24 and Siglec-10 in shaping the immunosuppressive tumour microenvironment and discuss the implications for combination therapies. Therefore, understanding the roles of CD24 and Siglec-10 in cancer immunotherapy opens exciting possibilities for the development of novel therapeutics.

UNASSIGNED: Breast cancer stem cells (BCSCs) as a kind of tumor cells are able to regenerate themselves, leading to apoptosis resistance and cancer relapse. It was reported that BCSCs contain lower levels of reactive oxygen species (ROS) associated with stemness capability. Caesalpinia sappan has been proposed for its chemopreventive potency against several cancer cells. This study aimed to evaluate the effects of Caesalpinia sappan extract (CSE) on cytotoxicity, apoptosis induction, ROS generation, and stemness markers of MDA-MB-231 and its BCSCs.
UNASSIGNED: Caesalpinia sappan was extracted under maceration with methanol. Magnetic-activated cell sorting was used to isolate BCSCs based on CD44+ and CD24- cell surface expression. The MTT test was used to assess the cytotoxic effects of CSE on MDA-MB-231 and BCSCs. Moreover, flow cytometry was used to examine the cell cycle distribution, apoptosis, ROS level, and CD44/CD24 level. Using qRT-PCR, the gene expression of the stemness markers NANOG, SOX-2, OCT-4, and c-MYC was assessed.
UNASSIGNED: We found that MDA-MB-231 contains 80% of the BCSCs population, and CSE showed more potent cytotoxicity toward BCSCs than MDA-MB-231. CSE caused apoptosis in MDA-MB-231 and BCSCs cells by increasing the level of ROS. Furthermore, CSE significantly reduced the MDA-MB-231 stemness marker CD44+/CD24- and the mRNA levels of pluripotent markers of cells in BCSCs.
UNASSIGNED: CSE potentially reduces BCSCs stemness, which may be mediated by the elevation of the ROS levels and reduction of the expression levels of stemness transcription.

BACKGROUND: CD24 is a highly glycosylated glycosylphosphatidylinositol anchored membrane protein that plays an important role in tumor progression. The aim of this study was to investigate the effect of abnormal expression of CD24 on the proliferation, migration and invasion of breast cancer (BC) cells, and the molecular mechanism of regulating CD24 expression in breast cancer.
METHODS: The bioinformatics method was used to predict the expression level of CD24 in BC and its relationship with the occurrence and development of BC. IHC, RT-qPCR and WB were used to detect the expression of CD24 in BC tissues and cells. The proliferation of CD24 was evaluated by CCK-8 and colony formation assay, and the migration and invasion of CD24 were evaluated by wound healing and transwell. In addition, the effect of CD24 on the malignancy of BC in vivo was further evaluated by subcutaneous tumorigenesis assay. Molecular mechanisms were measured by luciferase reporter assays, biotin-labeled miRNA pull-down assay, RIP, and western blotting.
RESULTS: The results show that CD24 is highly expressed in breast cancer tissues and cell lines, and knockdown of CD24 in vivo and in vitro can inhibit the proliferation, migration and invasion of BC cells. Mechanistically, the transcription factor ZNF460 promotes its expression by binding to the CD24 promoter, and the expression of ZNF460 is regulated by miR-125a-5p, which inhibits its expression by targeting the 3\'UTR of ZNF460. In addition, LINC00525 acts as a ceRNA sponge to adsorb miR-125a-5p and regulate its expression.
CONCLUSIONS: Overexpression of CD24 is involved in the development and poor prognosis of BC, which can be used as a potential target for the treatment of BC and provide a theoretical basis for the treatment of BC.

CD24 is a glycosylphosphatidylinositol-anchored protein that is expressed in a wide range of tissues and cell types. It is involved in a variety of physiological and pathological processes, including cell adhesion, migration, differentiation, and apoptosis. Additionally, CD24 has been studied extensively in the context of cancer, where it has been found to play a role in tumor growth, invasion, and metastasis. In recent years, there has been growing interest in CD24 as a potential therapeutic target for cancer treatment. This review summarizes the current knowledge of CD24, including its structure, function, and its role in cancer. Finally, we provide insights into potential clinical application of CD24 and discuss possible approaches for the development of targeted cancer therapies.

Increasing evidence suggests the importance of CD24 in tumor progression, but its role and mechanism in esophageal squamous cell carcinoma (ESCC) remain unclear. The present study aims to explore the potential of CD24 as a novel predictive biomarker in ESCC, as well as its mechanism and therapeutic implications in metastasis and 5-FU chemoresistance. By using tissue microarray and immunohistochemistry, we found that CD24 expression was higher in ESCC tumor tissues than paired non-tumor tissues, further indicating that CD24 was markedly associated with poor prognosis. CD24 significantly promoted metastasis and 5-FU chemoresistance in vitro and in vivo. Mechanistically, CD24 competes with GIT2 to bind to Arf6, and stabilizes Arf6-GTP to activate the subsequent ERK pathway, thus promoting cancer progression. In addition, a significant positive correlation between CD24 and p-ERK was observed in clinical ESCC tissues. In summary, this study not only reveals CD24 as a regulatory factor for Arf6 activity, but also uncovers CD24-Arf6-ERK signaling axis as a novel mechanism of ESCC progression. Our findings suggest CD24 as a promising biomarker and therapeutic target in ESCC.

L-type amino acid transporter 1 (LAT1) is specifically expressed in many malignancies, contributes to the transport of essential amino acids, such as leucine, and regulates the mammalian target of rapamycin (mTOR) signaling pathway. We investigated the expression profile and functional role of LAT1 in prostate cancer using JPH203, a specific inhibitor of LAT1. LAT1 was highly expressed in castration-resistant prostate cancer (CRPC) cells, including C4-2 and PC-3 cells, but its expression level was low in castration-sensitive LNCaP cells. JPH203 significantly inhibited [14C] leucine uptake in CRPC cells but had no effect in LNCaP cells. JPH203 inhibited the proliferation, migration, and invasion of CRPC cells but not of LNCaP cells. In C4-2 cells, Cluster of differentiation (CD) 24 was identified by RNA sequencing as a novel downstream target of JPH203. CD24 was downregulated in a JPH203 concentration-dependent manner and suppressed activation of the Wnt/β-catenin signaling pathway. Furthermore, an in vivo study showed that JPH203 inhibited the proliferation of C4-2 cells in a castration environment. The results of this study indicate that JPH203 may exert its antitumor effect in CRPC cells via mTOR and CD24.

BACKGROUND: Tumor immunotherapy brings new light and vitality to breast cancer patients, but low response rate and limitations of therapeutic targets become major obstacles to its clinical application. Recent studies have shown that CD24 is involved in an important process of tumor immune regulation in breast cancer and is a promising target for immunotherapy.
METHODS: In this study, singleR was used to annotate each cell subpopulation after t-distributed stochastic neighbor embedding (t-SNE) methods. Pseudo-time trace analysis and cell communication were analyzed by Monocle2 package and CellChat, respectively. A prognostic model based on CD24-related genes was constructed using several machine learning methods. Multiple quantitative immunofluorescence (MQIF) was used to evaluate the spatial relationship between CD24+PANCK+cells and exhausted CD8+T cells.
RESULTS: Based on the scRNA-seq analysis, 1488 CD24-related differential genes were identified, and a risk model consisting of 15 prognostic characteristic genes was constructed by combining the bulk RNA-seq data. Patients were divided into high- and low-risk groups based on the median risk score. Immune landscape analysis showed that the low-risk group showed higher infiltration of immune-promoting cells and stronger immune reactivity. The results of cell communication demonstrated a strong interaction between CD24+epithelial cells and CD8+T cells. Subsequent MQIF demonstrated a strong interaction between CD24+PANCK+ and exhausted CD8+T cells with FOXP3+ in breast cancer. Additionally, CD24+PANCK+ and CD8+FOXP3+T cells were positively associated with lower survival rates.
CONCLUSIONS: This study highlights the importance of CD24+breast cancer cells in clinical prognosis and immunosuppressive microenvironment, which may provide a new direction for improving patient outcomes.