Background: Lipolysis-stimulated lipoprotein receptor (LSR), a lipid receptor, is associated with cancer progression. However, detailed effects on intracellular metabolism are unclear. We aimed to elucidate the mechanism of LSR-mediated lipid metabolism in gastric cancer.
Methods: We investigated lipid metabolic changes induced by lipoprotein administration in gastric cancer cells and evaluated the significance of LSR expression and lipid droplets formation in gastric cancer patients. The efficacy of inhibiting β-oxidation in gastric cancer cells was also examined in vitro and vivo.
Results: In gastric cancer cells, LSR promoted cellular uptake of lipoprotein and cell proliferation. Furthermore, the inhibition of LSR in gastric cancer cells expressing high levels of LSR counteracted both effects. Immunohistochemical analysis of human gastric cancer tissues showed that the increase in lipid droplets via LSR is a factor that influences prognosis. Lipidomics analysis of LSR-high-expressing gastric cancer cells revealed an increase in β-oxidation. Based on these results, we used etomoxir, a β-oxidation inhibitor, and found that it inhibited cell proliferation as well as the suppression of LSR. Similarly, in a mouse xenograft model of LSR-highly expressing gastric cancer cells, the tumor growth effect of high-fat diet feeding was counteracted by etomoxir, consistent with the Ki-67 labeling index.
Conclusions: We demonstrated that lipids are taken up into gastric cancer cells via LSR and cause an increase in β-oxidation, resulting in the promotion of cancer progression. Controlling LSR-mediated lipid metabolism may be a novel therapeutic strategy for gastric cancer.
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http://dx.doi.org/10.1007/s10120-024-01552-z | DOI Listing |
Front Oncol
December 2024
The 5-year overall survival rate for stage IV gastric cancer is lower than 10%, despite the development of systemic therapy. Conversion surgery has shown to improve survival outcomes in patients with durable clinical response on chemotherapy. We report a clinical case of a patient, who underwent conversion surgery after pembrolizumab in the third-line setting for stage IV gastric cancer.
View Article and Find Full Text PDFFront Oncol
December 2024
Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
A 13-year-old boy was admitted to Xiang'an Hospital of Xiamen University due to HBV-related liver cancer. Intrahepatic metastasis was considered to occur by CT scan. A gastroscope revealed esophagogastric variceal bleeding, and later, the patient underwent a successful liver transplantation.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
December 2024
State Key Laboratory of Stress Cell Biology, School of Life Sciences; Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Xiamen 361102, China.
Gastric cancer (GC) is an aggressive tumor type with an intricate pathogenesis and limited therapeutic options. Ubiquitin-specific protease 22 (USP22) is a protein implicated in cell proliferation, metastasis, and tumorigenesis. However, the regulatory mechanisms governing USP22 in GC are still not fully understood.
View Article and Find Full Text PDFCurr Med Imaging
December 2024
Department of Radiology, Affiliated Hospital of Chengde Medical College, Chengde, China.
Objective: This study aimed to develop an automated method for segmenting spleen computed tomography (CT) images using a deep learning model to address the limitations of manual segmentation, which is known to be susceptible to inter-observer variability. Subsequently, a prediction model for gastric cancer (GC) differentiation was constructed alongside radiomics, and a nomogram was generated to investigate its clinical guiding significance.
Methods: This study enrolled 262 patients with pathologically confirmed GC.
BMC Med
December 2024
Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Background: Helicobacter pylori infection causes gastritis, peptic ulcers, and gastric cancer. The infection is typically acquired in childhood and persists throughout life. The major impediment to successful therapy is antibiotic resistance.
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