ArticleExperimental and therapeutic medicine2026
CDX2-UPK1B-PIK3IP1-PI3K/AKT signaling axis regulates gastric cancer cell invasion and migration and influences patient prognosis.
Article in Experimental and therapeutic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Gastric cancer (GC) remains one of the leading causes of cancer-related mortality worldwide, with malignant metastasis being a major determinant of patient prognosis. The metastatic process involves a number of phenotypic alterations, including enhanced invasive and migratory capacities. The growing availability of unbiased transcriptomic data has facilitated the identification of metastasis-associated molecular biomarkers and has enabled the exploration of their underlying mechanisms, with the aim of identifying novel therapeutic targets. In the present study, differential expression analysis was performed using The Cancer Genome Atlas Stomach Adenocarcinoma dataset to identify genes associated with malignant metastasis in GC. Prognostic signature genes were subsequently identified using Least Absolute Shrinkage and Selection Operator and Cox regression analyses. Western blotting, wound healing and Transwell assays were performed to investigate the association between gene expression, PI3K/AKT signaling activity, and GC cell invasion and migration. The interaction between uroplakin 1B (UPK1B) and PI3K inhibitor interacting protein 1 (PIK3IP1) was experimentally validated. A set of prognostic signature genes associated with the malignant metastasis of GC was identified, among which UPK1B and chorionic gonadotropin subunit β-5 were demonstrated to be independent predictors of a poor outcome. Notably, UPK1B was validated as an independent biomarker of poor prognosis and a potential therapeutic target in GC. Functional experiments revealed that UPK1B interacted with PIK3IP1 and attenuated the inhibitory effect of PIK3IP1 on the PI3K/AKT signaling pathway, thereby enhancing GC cell invasion and migration. In addition, caudal-related homeobox transcription factor 2 (CDX2) was identified as the transcriptional repressor of UPK1B. The present study delineated prognostic signature genes associated with malignant metastasis of GC. Among them, UPK1B served a pivotal role in regulating GC cell invasion and migration via the CDX2-UPK1B-PIK3IP1-PI3K/AKT axis. These findings provide novel insights into the molecular mechanisms underlying GC metastasis, and highlight UPK1B as a promising biomarker and therapeutic target for future GC therapies.
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