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Updated: Apr 14, 2026
Development and Maintenance of a Preclinical Patient Derived Tumor Xenograft Model for the Investigation of Novel Anti-Cancer Therapies
Published on: September 30, 2016
Targeting SLC5A2 suppresses colorectal tumour development by enhancing NK cell activity through extracellular
Jun Xiao1,2,3, Jianghua Wu1,3, Fengliu Deng4
1Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Abstract:
Tumour metabolic modulation represents a promising adjuvant therapeutic strategy for cancers, including colorectal cancer (CRC). Dapagliflozin, a clinically approved sodium‒glucose cotransporter 2 (SLC5A2/SGLT2) inhibitor, has attracted considerable attention, yet its functional role in CRC remains unclear. Here, we investigated the oncogenic effect of SLC5A2 on the colorectal mucosal epithelium using transgenic rats and an azoxymethane/dextran sulphate sodium (AOM/DSS)-induced tumour model. Multiple immunofluorescence and tissue microarray analyses of clinical samples revealed an inverse correlation between SLC5A2 expression and natural killer (NK) cell infiltration, highlighting the therapeutic potential of dapagliflozin for CRC treatment. Mechanistically, gene expression profiling analysis and coculture experiments demonstrated that SLC5A2 impairs NKG2D-mediated NK cell cytotoxicity. Furthermore, perforated patch‒clamp and calcium imaging revealed that SLC5A2 modulates the membrane potential and calcium influx, enhancing MHC-I-associated MICA/B secretion via extracellular vesicle (EV) formation and thereby enabling CRC cells to evade NK cell surveillance. Our findings reveal a critical oncogenic role of SLC5A2 in CRC progression and suggest dapagliflozin as a novel therapeutic option, particularly for CRC patients with metabolic comorbidities.
Insights
Sodium-glucose cotransporter 2 (SLC5A2/SGLT2) promotes colorectal cancer (CRC) by enabling tumor cells to evade natural killer (NK) cell attacks. Dapagliflozin may offer a new therapeutic strategy for CRC patients.
Area of Science:
- Oncology
- Immunology
- Metabolic Research
Background:
- Tumor metabolic modulation is a key therapeutic strategy for cancers like colorectal cancer (CRC).
- The role of sodium-glucose cotransporter 2 (SLC5A2/SGLT2) in CRC remains largely unknown.
- Dapagliflozin, an SLC5A2 inhibitor, is clinically approved but its function in CRC needs clarification.
Purpose of the Study:
- To investigate the oncogenic role of SLC5A2 in colorectal cancer.
- To explore the potential of dapagliflozin as a therapeutic agent for CRC.
- To elucidate the mechanisms by which SLC5A2 influences the tumor microenvironment and immune surveillance.
Main Methods:
- Utilized transgenic rats and an azoxymethane/dextran sulphate sodium (AOM/DSS) induced CRC model.
- Performed immunofluorescence, tissue microarray, gene expression profiling, and coculture experiments.
- Employed perforated patch-clamp and calcium imaging to analyze cellular mechanisms.
Main Results:
- Found an inverse correlation between SLC5A2 expression and natural killer (NK) cell infiltration in clinical CRC samples.
- Demonstrated that SLC5A2 impairs NKG2D-mediated NK cell cytotoxicity.
- Showed SLC5A2 enhances MICA/B secretion via extracellular vesicles (EVs), facilitating CRC cell evasion of NK cell surveillance.
Conclusions:
- SLC5A2 plays a critical oncogenic role in colorectal cancer progression.
- Dapagliflozin shows promise as a novel therapeutic option for CRC.
- This study highlights dapagliflozin's potential, especially for CRC patients with metabolic comorbidities.
