Open AccessCombined PGE2 with TNF-α promotes laryngeal carcinoma progression by enhancing GRK2 and TRAF2 interaction
Author(s) -
Y F Li,
Chunrong Han,
Y Wang,
Dongxu Cui,
Tianfei Luo,
Y W Zhang,
Yihui Ma,
Wen Wei
Publication year - 2020
Publication title -
neoplasma
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.628
H-Index - 50
eISSN - 1338-4317
pISSN - 0028-2685
DOI - 10.4149/neo_2020_190526n463
Subject(s) - tumor necrosis factor alpha , traf2 , cancer research , western blot , downregulation and upregulation , blot , immunohistochemistry , chemistry , signal transduction , crosstalk , cell growth , biology , medicine , microbiology and biotechnology , tumor necrosis factor receptor , biochemistry , gene , physics , optics
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.