PGE2 与 TNF-α 联合促进喉癌进展，增强 GRK2 与 TRAF2 相互作用。
Combined PGE2 with TNF-α promotes laryngeal carcinoma progression by enhancing GRK2 and TRAF2 interaction.
机构信息
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Collaborative Innovation Center of Anti-inflammatory and Immune Medicine, Hefei, China.
Department of Otorhinolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
出版信息
Neoplasma. 2020 Mar;67(2):354-363. doi: 10.4149/neo_2020_190526N463. Epub 2020 Jan 27.
TNF-α has been confirmed to promote tumor growth in LSCC. PGE2 expression in LSCC tissues was significantly higher than in tumor-adjacent tissues. In the present work, we aimed to discover the combined role of TNF-α and PGE2 in LSCC progression and its potential mechanisms. TNF-α and PGE2 were quantified by ELISA. TRAF2, MMP-9 and GRK2 expressions were detected by immunohistochemistry and western blot. UM-SCC-11A cell proliferation was tested by CCK-8, and cell migration and invasion were determined by transwell assay. GRK2/TRAF2 interaction was tested by Co-IP. The results showed that TNF-α, PGE2, TRAF2, MMP-9 and GRK2 expressions were significantly higher in tumor tissues than in tumor-adjacent tissues. Higher expressions of TRAF2, MMP-9 and GRK2 were associated with poorer prognosis of LSCC. Combined TNF-α with PGE2 promoted UM-SCC-11A cell proliferation, migration and invasion. The interactions of TRAF2 and GRK2, as well as MMP-9 expression, were upregulated in response to TNF-α and PGE2 co-stimulation. In conclusion, we found crosstalk between PGE2 and TNF-α signaling pathways, and the interaction between GRK2 and TRAF2 led to the activation of TNF-α-TRAF2-MMP-9 signaling and resulted in the progression of LSCC.
TNF-α 已被证实可促进 LSCC 中的肿瘤生长。LSCC 组织中的 PGE2 表达明显高于肿瘤邻近组织。在本工作中，我们旨在发现 TNF-α 和 PGE2 在 LSCC 进展中的联合作用及其潜在机制。通过 ELISA 定量检测 TNF-α 和 PGE2。通过免疫组织化学和 Western blot 检测 TRAF2、MMP-9 和 GRK2 的表达。通过 CCK-8 检测 UM-SCC-11A 细胞增殖，通过 Transwell 测定细胞迁移和侵袭。通过 Co-IP 检测 GRK2/TRAF2 相互作用。结果表明，TNF-α、PGE2、TRAF2、MMP-9 和 GRK2 的表达在肿瘤组织中明显高于肿瘤邻近组织。TRAF2、MMP-9 和 GRK2 的高表达与 LSCC 的预后较差相关。TNF-α 与 PGE2 联合促进了 UM-SCC-11A 细胞的增殖、迁移和侵袭。TRAF2 和 GRK2 的相互作用以及 MMP-9 的表达在 TNF-α 和 PGE2 共同刺激下上调。总之，我们发现 PGE2 和 TNF-α 信号通路之间存在串扰，GRK2 和 TRAF2 之间的相互作用导致 TNF-α-TRAF2-MMP-9 信号的激活，从而导致 LSCC 的进展。
Zotero 插件