DUSP5 suppresses esophageal squamous cell carcinoma by counteracting macrophage-derived AREG-ERK1/2 signaling and disrupting an oncogenic ERK1/2-ELK1-DUSP5 feedback circuitry
The canonical text that states the DUSP5 expression is downregulated in ESCC tissues and that its overexpression inhibits tumor growth is:
Dual‑specificity phosphatase 5 (DUSP5) is a key regulator of the MAPK pathway. In esophageal squamous cell carcinoma (ESCC), single‑cell RNA sequencing revealed macrophage populations that engage tumor cells via an AREG‑EGFR axis to activate ERK signaling. DUSP5 was down‑regulated in ESCC tissues; overexpression inhibited proliferation, induced senescence and apoptosis, and suppressed migration and invasion. In xenograft models, DUSP5 overexpression reduced tumor growth and metastasis, while ERK1/2 activation reversed its tumor‑suppressive effects. ELK1, an ERK1/2 downstream transcription factor, negatively regulates DUSP5. In a carcinogen‑induced model, DUSP5 knockout increased tumor burden, an effect reversed by ERK1/2 inhibition. These findings highlight the DUSP5‑ERK1/2‑ELK1 axis as a driver of ESCC progression and a potential therapeutic target.
Understanding how DUSP5 modulates ERK signaling in esophageal squamous cell carcinoma clarifies a novel tumor‑suppressive pathway and offers potential biomarkers or therapeutic targets for this aggressive malignancy.
Evidence level: Korai humán adat. Kis vagy feltáró emberi adat.
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