EP4 stimulation promotes cell adhesion and migration via IL-6 signaling in oral squamous cell carcinoma
Wakana Fukae, Soichiro Ishikawa, Yu Iida, Akane Nagasako, Michiko Endo, Chihiro Hayashi, Kagemichi Nagao, Sneri Oguri, Takayuki Fujita, Utako Yokoyama, Kenji Mitsudo, Yoshihiro Ishikawa, Masanari Umemura
TL;DR
This study shows that activating the EP4 receptor increases cell adhesion and migration in oral cancer cells through the IL-6 signaling pathway.
Contribution
The novel finding is that EP4 promotes cell adhesion and migration in OSCC via IL-6 signaling.
Findings
EP4 stimulation increases IL-6 mRNA and protein secretion in OSCC cells.
PGE₂ promotes cell adhesion and migration through EP4 and IL-6.
Blocking EP4 or IL-6 inhibits these effects.
Abstract
Oral squamous cell carcinoma cell (OSCC) comprises malignant neoplasms arising within the oral cavity. Early-stage detection is associated with favorable prognosis, whereas progression to advanced stages with lymph node metastasis significantly worsens outcomes. We previously reported that the prostaglandin E₂ (PGE₂) receptor EP4 regulates OSCC migration. RNA sequencing reanalysis suggested that EP4 stimulation is strongly associated with cell migration and adhesion, with interleukin-6 (IL-6) emerging as a central mediator of these processes. In OSCC cells, ONO-AE1–437 (EP4 agonist) increased IL-6 mRNA expression and protein secretion. EP4-overexpressing cells showed increased IL-6 expression without stimulation, further enhanced by ONO-AE1–437 or PGE₂. xCELLigence demonstrated that PGE₂ promoted cell adhesion, which was suppressed by ONO-AE3–208 (EP4 antagonist) and Tocilizumab (IL-6…
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Taxonomy
TopicsInflammatory mediators and NSAID effects · Cancer, Stress, Anesthesia, and Immune Response · Tannin, Tannase and Anticancer Activities