國家衛生研究院 NHRI:Item 3990099045/16280
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    題名: Cooperative participation of CagA and NFATc1 in the pathogenesis of antibiotics-responsive gastric MALT lymphoma
    作者: Tsai, HJ;Yeh, KH;Lin, CW;Wu, MS;Liou, JM;Hsu, PN;Zeng, YS;Wei, MF;Shun, CT;Wang, HP;Chen, LT;Cheng, AL;Kuo, SH
    貢獻者: National Institute of Cancer Research
    摘要: BACKGROUND: This study aimed to explore whether cytotoxin-associated gene A (CagA) can inhibit cell cycle progression by activating nuclear factor of activated T cells (NFAT) in lymphoma B cells and contribute to Helicobacter pylori eradication (HPE) responsiveness (complete remission [CR] after HPE) in gastric mucosa-associated lymphoid tissue (MALT) lymphoma. MATERIALS AND METHODS: We co-cultured three B-lymphoma cell lines (MA-1, OCI-Ly3, and OCI-Ly7) with HP strains (derived from HPE-responsive gastric MALT lymphoma) and evaluated the expression patterns of CagA, phosphorylated (p)-CagA (CagA(P-Tyr)), and CagA-signaling molecules, cell-cycle inhibitors, p-NFATc1 (Ser(172)), and NFATc1 using western blotting. Furthermore, we evaluated the association between nuclear NFATc1 expression in the tumor cells of 91 patients who received first-line HPE (59 patients with HPE responsiveness and 32 without HPE responsiveness) and HPE responsiveness and CagA expression in tumor cells. RESULTS: In HP strains co-cultured with B cell lymphoma cell lines, CagA was translocated to the nucleus through tyrosine phosphorylation (CagA(P-Tyr)) and simultaneously dephosphorylated NFATc1, subsequently causing nuclear NFATc1 translocation and stimulating the expression of p-SHP-2/p-ERK/Bcl-xL. Activated NFATc1 causes G1 cell cycle retardation in both MA-1 and OCI-Ly3 cells by triggering p21 and p27 production. Nuclear NFATc1 localization was significantly associated with the presence of CagA in gastric MALT lymphomas (80% [41/51] vs. 33% [13/40]; p < 0.001) and with HPE responsiveness (73% [43/59] vs. 25% [8/32]; p < 0.001). Patients exhibiting both the presence of CagA and nuclear NFATc1 localization responded more rapidly to HPE than those without (median interval to CR, 4.00 vs. 6.00 months, p = 0.003). CONCLUSIONS: Our findings indicated that CagA and NFATc1 cooperatively participate in the lymphomagenesis of HPE-responsive gastric MALT lymphoma.
    日期: 2024-11-18
    關聯: Cancer Cell International. 2024 Nov 18;24:Article number 383.
    Link to: http://dx.doi.org/10.1186/s12935-024-03552-6
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1475-2867&DestApp=IC2JCR
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85209538700
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