AI Article Synopsis
- FPR3 regulates gastric cancer (GC) progression by inhibiting aerobic glycolysis and the stemness of tumor cells, which are key factors in cancer growth and resistance to therapy.
- The mechanism involves FPR3's effect on calcium ion flux and the inhibition of NFATc1, which disrupts the expression of NOTCH3 and influences the AKT/mTORC1 signaling pathway.
- This study suggests that targeting FPR3 could offer new strategies for cancer treatment by modifying the metabolic and stem cell properties of GC cells.
Article Abstract
Aerobic glycolysis accelerates tumor proliferation and progression, and inhibitors or drugs targeting abnormal cancer metabolism have been developing. Cancer stem-like cells (CSCs) significantly contribute to tumor initiation, metastasis, therapy resistance, and recurrence. Formyl peptide receptor 3 (FPR3), a member of FPR family, involves in inflammation, tissue repair, and angiogenesis. However, studies in exploring the regulatory mechanisms of aerobic glycolysis and CSCs by FPR3 in gastric cancer (GC) remain unknown. Here, we demonstrated that overexpressed FPR3 suppressed glycolytic capacity and stemness of tumor cells, then inhibited GC cells proliferation. Mechanistically, FPR3 impeded cytoplasmic calcium ion flux and hindered nuclear factor of activated T cells 1 (NFATc1) nuclear translocation, leading to the transcriptional inactivation of NFATc1-binding neurogenic locus notch homolog protein 3 (NOTCH3) promoter, subsequently obstructing NOTCH3 expression and the AKT/mTORC1 signaling pathway, and ultimately downregulating glycolysis. Additionally, NFATc1 directly binds to the sex determining region Y-box 2 (SOX2) promoter and modifies stemness in GC. In conclusion, our work illustrated that FPR3 played a negative role in GC progression by modulating NFATc1-mediated glycolysis and stemness in a calcium-dependent manner, providing potential insights into cancer therapy.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.canlet.2024.216841 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Efficacy of robot-assisted double-flap techniques with refinements to minimize anastomosis-related complications after proximal gastrectomy.
Surg Today
January 2025
Department of Gastroenterological Surgery, Hyogo Medical University, 1-1 Mukogawa, Nishinomiya, Hyogo, 663-8501, Japan.
Purpose: The double-flap technique (DFT) is an anti-reflux reconstruction procedure performed after proximal gastrectomy (PG), but its complexity and high incidence of anastomotic stenosis are problematic. We conducted this study to demonstrate the efficacy of robot-assisted DFT, with refinements, to address these issues.
Methods: Surgical outcomes were compared between the following procedures modified over time at our institution: conventional open DFT (group O, n = 16); early robotic DFT (group RE, n = 19), which follows the conventional open PG approach; and late robotic DFT (group RL, n = 21), which incorporates refinements to the early robotic DFT technique by exploiting more of the robotic capabilities available.
Unraveling the Role of Ubiquitin-Conjugating Enzyme UBE2T in Tumorigenesis: A Comprehensive Review.
Cells
December 2024
State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-Products, School of Marine Sciences, Ningbo University, Ningbo 315211, China.
Ubiquitin-conjugating enzyme E2 T (UBE2T) is a crucial E2 enzyme in the ubiquitin-proteasome system (UPS), playing a significant role in the ubiquitination of proteins and influencing a wide range of cellular processes, including proliferation, differentiation, apoptosis, invasion, and metabolism. Its overexpression has been implicated in various malignancies, such as lung adenocarcinoma, gastric cancer, pancreatic cancer, liver cancer, and ovarian cancer, where it correlates strongly with disease progression. UBE2T facilitates tumorigenesis and malignant behaviors by mediating essential functions such as DNA repair, apoptosis, cell cycle regulation, and the activation of oncogenic signaling pathways.
View Article and Find Full Text PDFBackground: There is controversy regarding which is the best reconstruction technique after the pancreatoduodenectomy. Currently, there are no studies comparing the three most frequent reconstruction techniques: Whipple + Roux-en-Y gastrojejunostomy (WRYGJ), pyloric-preserving + Billroth II (PPBII), and Whipple + BII (WBII).
Methods: Between 2012 and March 2023, 246 patients underwent pancreaticoduodenectomy with the following type of reconstruction techniques: (1) WRYGJ: 40 patients; (2) PPBII: 118 patients; and (3) WBII: 88 patients.
Ethnic Inequity in the Current Approach to H. pylori Testing and Treatment: Linked Data Cohort Analysis.
Helicobacter
January 2025
Department of Public Health, University of Otago, Wellington, South, New Zealand.
Background: As seen globally, there are up to sixfold differences in gastric cancer mortality by ethnicity in Aotearoa New Zealand, and H. pylori is the major modifiable risk factor. This study investigates whether current H.
View Article and Find Full Text PDFRNA Modification and Digestive Tract Tumors: A Review.
Curr Med Chem
January 2025
Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, 471000, Henan, China.
Gastrointestinal tumors, including colorectal and liver cancer, are among the most prevalent and lethal solid tumors. These malignancies are characterized by worsening prognoses and increasing incidence rates. Traditional therapeutic approaches often prove ineffective.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!