The IL1β-NFκB-SDC4 signaling Axis promotes esophageal cancer cell proliferation and is suppressed by EGCG

  • Cell Signal. 2026 Apr:140:112365. doi: 10.1016/j.cellsig.2026.112365.
Fei Zhou  1 ,  Yuanduo Li  2 ,  Xiaotong Liang  2 ,  Xiaoru Xie  2 ,  Wenzhang Zheng  2 ,  Zikai Chen  1 ,  Xianghui Zou  1 ,  Zhicong Liu  1 ,  Feng Pan  3 ,  Hui Zhu  4 ,  Yuzhong Zheng  5
Affiliations
  • 1. Guangdong Provincial Key Laboratory of Functional Substances in Medicinal Edible Resources and Healthcare Products, Hanshan Normal University, Chaozhou 521041, China.
  • 2. Department of Cell Biology, Hanshan Normal University, Chaozhou 521041, China.
  • 3. Clinical Research Center, Shantou Central Hospital, Shantou 515041, China.
  • 4. Guangdong Provincial Key Laboratory of Functional Substances in Medicinal Edible Resources and Healthcare Products, Hanshan Normal University, Chaozhou 521041, China. Electronic address: [email protected].
  • 5. Guangdong Provincial Key Laboratory of Functional Substances in Medicinal Edible Resources and Healthcare Products, Hanshan Normal University, Chaozhou 521041, China. Electronic address: [email protected].
PMID: 41534677 DOI: 10.1016/j.cellsig.2026.112365
Abstract

Chronic inflammation promotes Esophageal Cancer (EC) progression through NFκB activation, yet the downstream effector genes driving EC progression remain incompletely characterized. Here, we identify syndecan-4 (SDC4) as a new NFκB target gene that is upregulated in EC and associated with poor prognosis. The pro-inflammatory cytokine IL1β stimulates EC cell proliferation and concurrently induces SDC4 expression in an NFκB-dependent manner. Mechanistically, NFκB directly binds to the SDC4 promoter region, which is enriched with the active chromatin marker H3K27Ac. Functional studies demonstrate that SDC4 is necessary for IL1β-driven proliferation, as its knockdown suppresses, whereas overexpression enhances EC cell proliferation. Notably, the natural compound epigallocatechin gallate (EGCG) effectively blocks this IL1β-NFκB-SDC4 axis by inhibiting NFκB nuclear translocation, thereby attenuating SDC4 upregulation and subsequent EC cell proliferation. Our findings establish SDC4 as a critical molecular link between inflammation and EC progression, and highlight EGCG as a potential therapeutic candidate targeting this pathway.

Keywords
Cell proliferation; EGCG; Esophageal cancer; NFκB; Syndecan-4.
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