SDCBP competes with CBL to stabilize PES1 and promote c-Myc translation in ESCC tumorigenesis.

SDCBP directly binds PES1 and stabilizes it by competitively disrupting PES1’s interaction with CBL, enhancing c-Myc translation in ESCC.

• Why it matters: SDCBP is linked to ESCC prognosis, but its interacting partners and oncogenic mechanism were unclear, limiting therapeutic targeting.
• What they did: The study mapped SDCBP–PES1 binding, showed SDCBP inhibits PES1 ubiquitination/degradation, and tested SDCBP loss in a 4NQO-induced murine model; it also used cRGD-LNPs-SDCBP-ASO in PDXs.
• The result: SDCBP ablation suppressed tumor initiation and progression in mice, and cRGD-LNPs-SDCBP-ASO tumor-targeted silencing inhibited the SDCBP–PES1–c-Myc axis and PDX tumor growth without apparent toxicity.

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