Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anti-SLC7A11 monoclonal antibody Inhibits Tumor Progression through a Janus-faced Effect on CD4+ and CD8+ T Cells in Colorectal Cancer [RNA-seq]

ABSTRACT: SLC7A11 is aberrantly overexpressed in numerous solid tumors, including colorectal cancer (CRC), where it serves as a key regulator of cystine import and ferroptosis. However, its therapeutic potential and feasible targeting strategies remain less well understood. Our findings reveal that elevated SLC7A11 expression is critical for the activation of regulatory T cells and is associated with advanced tumor grade, lymphatic metastasis, and poor prognosis in CRC patients. A monoclonal antibody that blocks the transporter function of SLC7A11 induces apoptosis across multiple cancer cell types and demonstrates significant therapeutic efficacy in preclinical mouse models of colon cancer. Additionally, inhibition of SLC7A11 reprograms the tumor immune microenvironment, transforming it from a 'cold' to a more immunogenic state by suppressing regulatory T cell activation. These results highlight the dual role of SLC7A11 in modulating CD4+ and CD8+ T cell responses, positioning SLC7A11 as a crucial orchestrator of tumor immune evasion and a promising therapeutic target.

ORGANISM(S): Homo sapiens

PROVIDER: GSE316624 | GEO | 2026/04/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Anti-SLC7A11 monoclonal antibody Inhibits Tumor Progression through a Janus-faced Effect on CD4+ and CD8+ T Cells in Colorectal Cancer [scRNA-seq]

Project description:SLC7A11 is aberrantly overexpressed in numerous solid tumors, including colorectal cancer (CRC), where it serves as a key regulator of cystine import and ferroptosis. However, its therapeutic potential and feasible targeting strategies remain less well understood. Our findings reveal that elevated SLC7A11 expression is critical for the activation of regulatory T cells and is associated with advanced tumor grade, lymphatic metastasis, and poor prognosis in CRC patients. A monoclonal antibody that blocks the transporter function of SLC7A11 induces apoptosis across multiple cancer cell types and demonstrates significant therapeutic efficacy in preclinical mouse models of colon cancer. Additionally, inhibition of SLC7A11 reprograms the tumor immune microenvironment, transforming it from a 'cold' to a more immunogenic state by suppressing regulatory T cell activation. These results highlight the dual role of SLC7A11 in modulating CD4+ and CD8+ T cell responses, positioning SLC7A11 as a crucial orchestrator of tumor immune evasion and a promising therapeutic target.

2026-04-01 | GSE316623 | GEO

Super-enhancer-driven MLX mediates redox balance maintanance via SLC7A11 in osteosarcoma

Project description:A systematic analysis of super-enhancers identified MLX as a potential oncogene in osteosarcoma. Knockdown of MLX impaired tumor aggressiveness in vitro and in vivo, suggesting oncogenic properties of MLX. Mechanistically, silencing of MLX downregulates SLC7A11, a key gene encoding glutamate/cystine antiporter, to attenuate the uptake of cystine and interrupt the redox balance, leading to ferroptotic cell death. Pharmacological inhibition of SLC7A11 triggered massive ferroptosis and caused impaired tumor growth, providing a promising approach for osteosarcoma treatment.

2023-08-08 | GSE220173 | GEO

TRIB3 inhibition by palbociclib sensitizes prostate cancer to ferroptosis via SOX2-mediated SLC7A11 downregulation

Project description:Palbociclib is a CDK4/6 inhibitor approved for the treatment of breast cancer by suppressing cell proliferation. However, monotherapy with palbociclib was discouraging in prostate cancer, calling for a mechanism-based effective therapy. In this study, we reported in prostate cancer that palbociclib is a potent sensitizer of ferroptosis, which is worked out by downregulating the expression of TRIB3, a gene highly expressed in prostate cancer. Specifically, TRIB3 knockdown augmented the response of prostate cancer cells to ferroptosis inducers, whereas, TRIB3 overexpression rescued prostate cancer cells from palbociclib-induced ferroptosis. Mechanistically, TRIB3 inhibition by palbociclib resulted in downregulation of SOX2, which subsequently led to compromised expression of SLC7A11, a cystine/glutamate antiporter that counteracts ferroptosis. Functionally, a combined treatment of palbociclib with ferroptosis inducer significantly suppressed prostate cancer growth in a xenograft tumor model. Together, these results uncover an essential role of TRIB3/SOX2/SLC7A11 axis in palbociclib-induced ferroptosis, suggesting palbociclib a promising targeted therapy in combine with ferroptosis induction for the treatment of prostate cancer.

2024-10-31 | GSE273622 | GEO

BAP1 links epigenetic regulation of ferroptosis to tumor suppression

Project description:Compared to the well-established roles of apoptosis in tumor suppression, the roles and regulatory mechanisms of ferroptosis, a non-apoptotic form of cell death, in tumor biology remain much less understood. BRCA1-associated protein 1 (BAP1) encodes a nuclear de-ubiquitinating (DUB) enzyme to reduce histone 2A ubiquitination (H2Aub) on chromatin, and is a tumor suppressor in several human cancers. Here, integrated transcriptomic, epigenomic, and cancer genomic analyses link BAP1 to metabolism-related biological processes, including oxidative stress response, and identify cystine transporter SLC7A11 as a BAP1-repressed target gene with high relevance to BAP1-mediated tumor suppression in human cancers. Functional studies reveal that BAP1, in a DUB-dependent manner, decreases H2Aub occupancy on the SLC7A11 promoter and represses SLC7A11 expression, and that BAP1 inhibits cystine uptake and promotes ferroptosis through repressing SLC7A11 expression. Finally, we show that BAP1 inhibits tumor development partly through SLC7A11, and that cancer-associated BAP1 mutants lose their abilities to repress SLC7A11 and to promote ferroptosis. Together, the results of our study show that BAP1 executes its tumor suppression function at least partly through its regulation of SLC7A11 and ferroptosis, and uncover a previously unappreciated mechanism coupling ferroptosis to tumor suppression.

2018-07-05 | GSE101987 | GEO

A novel MYC-ZNF706-SLC7A11 regulatory circuitry contributes to cancer progression and redox balance in human hepatocarcinoma (ChIP-Seq)

Project description:ZNF706 belongs to a member of C2H2-type zinc finger proteins which exerts pivotal roles in cancer progression. However, the biological function and mechanism of ZNF706 are rarely investigated. Using qRT-PCR and Western blot assays, we identified ZNF706 was frequently amplified in human hepatocarcinoma and high ZNF706 expression was associated with unfavorable HCC patient survival based on TCGA database. In vitro and in vivo experiments revealed that ZNF706 promoted HCC cell growth. Mechanistically, RNA-seq and ChIP-seq identified SLC7A11 was a critical target of ZNF706, and depletion of ZNF706 increased lipid peroxidation, cell death and decreased cystine uptake medicated by SLC7A11 contributing to redox homeostasis disruption. Furthermore, using luciferase report assays and ChIP-qPCR, we found MYC could regulate ZNF706 transcription by binding to ZNF706 promoter region, and further assay indicated MYC also involved in redox balance by modulating SLC7A11. Collectively, our study uncovers that the oncogenic role of ZNF706 in liver cancer, indicating that ZNF706 inhibition could be a potential treatment strategy for liver cancer.

2024-06-17 | GSE246331 | GEO

A novel MYC-ZNF706-SLC7A11 regulatory circuitry contributes to cancer progression and redox balance in human hepatocarcinoma (RNA-Seq)

2024-06-17 | GSE246330 | GEO

IGF2BP3 enhances ferroptosis resistance in colon cancer by stabilizing SLC7A11 mRNA and is regulated by miR-98-5p

Project description:Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, with increasing incidence and mortality rates. Resistance to cell death is a hallmark of cancer, and ferroptosis, a form of non-apoptotic cell death, has emerged as a critical factor in tumor suppression. The RNA-binding protein IGF2BP3, which plays a significant role in colon cancer progression, has been shown to modulate various oncogenic processes. However, its involvement in ferroptosis regulation in colon cancer remains largely unexplored. This study investigates the role of IGF2BP3 in ferroptosis regulation and its potential as a therapeutic target in colon cancer. Our data show that IGF2BP3 is upregulated in colon cancer tissues and correlates with poor prognosis. Knockdown of IGF2BP3 in colon cancer cell lines enhances sensitivity to ferroptosis induction, evidenced by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels, which are reversed by the ferroptosis inhibitor ferrostatin-1. Mechanistically, IGF2BP3 regulates ferroptosis by stabilizing SLC7A11 mRNA, a key ferroptosis regulator, through its interaction with the mRNA. Additionally, miR-98-5p directly targets IGF2BP3, enhancing ferroptosis sensitivity. In vivo studies confirm that IGF2BP3 knockdown suppresses tumor growth, highlighting its potential as a therapeutic target. Overall, our findings suggest that IGF2BP3 plays a pivotal role in regulating ferroptosis in colon cancer, offering new avenues for therapeutic strategies in colon cancer treatment.

2025-02-21 | GSE289758 | GEO

Chemerin attenuates acute kidney injury by inhibiting ferroptosis via the AMPK/NRF2/SLC7A11 axis

Project description:Acute kidney injury (AKI) is a common and life-threatening condition associated with cell death, where ferroptosis plays a critical role. Chemerin, primarily produced in white adipose tissue, has multiple biological functions in renal pathophysiology. However, to date, whether and how chemerin regulates the progression of AKI remain unclear. Here, we found that chemerin expression was reduced in both AKI model mice and cells. Similarly, serum chemerin levels were also decreased in AKI patients. The administration of recombinant chemerin improves renal function in ischemia-reperfusion (I/R) model mice. Chemerin significantly attenuates ferroptosis in kidneys. In TCMK-1 cells, chemerin knockdown further aggravates ferroptosis. Mechanistically, chemerin activates AMP-activated protein kinase (AMPK), which induces the phosphorylation of nuclear factor erythroid 2-related factor 2 (NRF2) in renal tubular cells. Subsequently, NRF2 translocates into the nucleus, where it stimulates the expression of cystine/glutamate antiporter solute carrier (SLC7A11). As a result, cystine uptake and glutathione (GSH) biosynthesis in renal tubular cells were increased, which confers cells with higher capacity against ferroptosis. Overall, our findings indicate that chemerin plays a protective role in AKI by repressing ferroptosis in renal tubular cells, which is likely due to the activation in the AMPK/NRF2/SLC7A11 axis.

2024-12-01 | GSE283126 | GEO

Hypoxia-induced cysteine metabolism reprogramming are crucial for the tumorigenesis of colorectal cancer [tissue pair]

Project description:Metabolic reprogramming is a hallmark of human cancer and cancer-specific metabolism provide opportunities for cancer diagnosis, prognosis, and treatment. However, how metabolic pathways affect the initiation and progression of colorectal cancer remain largely unknown. Here, we showed cysteine is highly enriched in colorectal tumors compared with adjacent non-tumor tissues to promote tumorigenesis of CRC. Both cystine and cysteine imports are essential to maintain intracellular cysteine level and promote tumor growth and survival. Transporter genes of cystine and cysteine are all upregulated in colorectal cancer by tumor microenvironment induced ROS through transcription factor ATF4. Glutathione synthetase GSS is upregulated and increases cysteine to reduced glutathione flux to support tumor growth and survival in colorectal cancer. Depletion of cystine and cysteine by a recombinant cyst(e)inase effectively reduced the growth of colorectal tumors. Moreover, scavenging cystine and cysteine induces autophagy of colorectal cancer cells through mTOR-ULK signaling axis. With this study, we demonstrate that cysteine metabolism is a key signature of CRC metabolic reprogramming and targeting cysteine metabolism might be an effective approach to treat colon cancer.

2023-01-21 | GSE223119 | GEO

Hypoxia-induced cysteine metabolism reprogramming are crucial for the tumorigenesis of colorectal cancer [HCT116]

2023-01-21 | GSE223118 | GEO