2. Academic Validation
  3. The IL1β-NFκB-SDC4 signaling Axis promotes esophageal cancer cell proliferation and is suppressed by EGCG

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

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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