ArticleCancer cell international2023
NUAK1 promotes tumor metastasis through upregulating slug transcription in esophageal squamous cell carcinoma.
Article in Cancer cell international, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 9 citations in OpenAlex.
- NUAK1 silencing enhances radiotherapy-induced ferroptosis in locally advanced rectal cancer by impairing Nrf2-driven transcription of GPX4.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Transposable Element-Derived miR-28-5p and miR-708-5p: Exploring Potential Roles in Lung Cancer.Non-coding RNA · 2025Article
- NUAK: never underestimate a kinase.Essays in biochemistry · 2024Review
- Evaluation of ARK5 and SIRT3 expression in renal cell carcinoma and their clinical significance.Diagnostic pathology · 2023Article
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMetastasis is still a major cause of poor pathological outcome and prognosis in esophageal squamous cell carcinoma (ESCC) patients. NUAK1 has been reported highly expressed in many human cancers and is associated with the poor prognosis of cancer patients. However, the role of NUAK1 and its underlying signaling mechanism in ESCC metastasis remain unclear.
methodsExpression of NUAK1 in ESCC was detected by real-time quantitative RT-PCR (qRT-PCR), Western blotting and immunohistochemical staining. MTT, colony formation, wound-healing and transwell assays were used to determine the role NUAK1 in vitro. Metastasis was evaluated by use of an experimental pulmonary metastasis model in BALB/c-nu/nu mice. The mechanisms were assessed by using coimmunoprecipitation, immunofluorescence and dual-luciferase reporter gene experiments.
resultsNUAK1 was highly expressed in ESCC tissues compared with the adjacent normal esophageal epithelial tissues. Moreover, the elevated expression of NUAK1 positively correlated with tumor invasion depth, lymph node metastasis, pathological TNM stage, and poor survival in ESCC patients. Further experiments showed that NUAK1 overexpression did not change the cell viability and colony formation of ESCC cells, while remarkably promoted the migration and invasion in vitro and experimental pulmonary metastasis in vivo. Mechanistically, NUAK1 enhanced the transcription level of Slug, which enhanced the migratory and invasive capability of ESCC cells. Consistently, silencing Slug almost completely diminished the migration and invasion of NUAK1-overexpressing ESCC cells. Further studies demonstrated that NUAK1 upregulated the transcription activity of Slug through activating the JNK/c-Jun pathway.
conclusionThese results demonstrated that NUAK1 promoted the metastasis of ESCC cells through activating JNK/c-Jun/Slug signaling, indicating NUAK1 is a promising therapeutic target for metastatic ESCC.
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