E74-like E26 transformation-specific transcription factor 3 in gastric cancer: Functions, mechanisms, and clinical translation - unresolved issues

Figure 1 Schematic illustration of the dual role of E74-like E26 transformation-specific transcription factor 3 in gastric cancer progression. A: E74-like E26 transformation-specific transcription factor 3 (ELF3) binds the CDH1 promoter to inhibit E-cadherin expression, inducing epithelial-mesenchymal transition; B: ELF3 binds the CXCL11 promoter to inhibit its expression, impairing CD8+ T cell recruitment. This figure is based on the model proposed by Sun et al[21], which presently has support from binding evidence and correlational data, but functional validation remains to be supplemented. The diagram is drawn by Figdraw (www.figdraw.com). EMT: Epithelial-mesenchymal transition; ELF3: E74-like E26 transformation-specific transcription factor 3; CTL: Cytotoxic T lymphocyte.

Figure 2 Potential therapeutic strategies that target E74-like E26 transformation-specific transcription factor 3. A: Direct targeting strategies: Small molecule inhibitors (e.g., YK1) disrupt the E74-like E26 transformation-specific transcription factor 3 (ELF3)-MED23 interaction, inhibiting ELF3 transcriptional activity, with proof-of-concept established in colorectal cancer[11,55]; B: Indirect targeting strategies: Restoring the E-cadherin expression to reverse epithelial-mesenchymal transition, or restoring the CXCL11 expression to enhance cytotoxic T lymphocyte recruitment, presently at the theoretical exploration stage; C: Combination therapy approach: Combining ELF3-targeted agents with immune checkpoint inhibitors may produce synergistic effects in preclinical models. This figure is based on existing literature[11,59,64]. The above strategies await systematic evaluation in gastric cancer. The diagram is drawn by Figdraw (www.figdraw.com). EMT: Epithelial-mesenchymal transition; ELF3: E74-like E26 transformation-specific transcription factor 3.