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CPNE3 promotes colorectal cancer progression by regulating KIF4-mediated autophagy.

Journal of gastrointestinal oncology 2026 Vol.17(1) p. 17

Tang C, Teng W, Jiang Y, Wu Y

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[BACKGROUND] Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide.

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APA Tang C, Teng W, et al. (2026). CPNE3 promotes colorectal cancer progression by regulating KIF4-mediated autophagy.. Journal of gastrointestinal oncology, 17(1), 17. https://doi.org/10.21037/jgo-2025-735
MLA Tang C, et al.. "CPNE3 promotes colorectal cancer progression by regulating KIF4-mediated autophagy.." Journal of gastrointestinal oncology, vol. 17, no. 1, 2026, pp. 17.
PMID 41816564

Abstract

[BACKGROUND] Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide. This study examines the role of CPNE3 in CRC progression and its interaction with KIF4 to identify potential therapeutic targets.

[METHODS] We identified CPNE3 as a candidate oncogene using bioinformatics. Its expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in CRC tissues and cell lines. The effects of CPNE3 on proliferation, colony formation, migration, invasion, apoptosis, and autophagy were tested with gain- and loss-of-function experiments. Co-immunoprecipitation (IP), immunofluorescence, and Biological General Repository for Interaction Datasets (BIOGRID) analysis were used to find interacting proteins and pathways. KIF4 knockdown was performed to confirm functional rescue.

[RESULTS] CPNE3 was upregulated in CRC. Silencing it reduced proliferation, migration, and invasion, and increased apoptosis and autophagy. Overexpression had opposite effects, increased KIF4 levels, activated PI3K/AKT/mTOR signaling, and suppressed autophagy markers (ATG5, ATG7, P62, LC3-II). CPNE3 directly interacted with KIF4. Knocking down KIF4 reversed the oncogenic effects of CPNE3 overexpression.

[CONCLUSIONS] CPNE3 promotes CRC progression by interacting with KIF4 and regulating PI3K/AKT/mTOR and autophagy pathways. The CPNE3-KIF4 axis is a potential therapeutic target.

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