ArticleJournal of experimental & clinical cancer research : CR2025
Copy number amplification of TTPAL promotes cholesterol biosynthesis and esophageal squamous cell carcinoma progression via elevating NSUN2-mediated m5C modification of SREBP2 mRNA.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- NSUN2-mediated m5C modification of E2F1 promotes lung adenocarcinoma progression via the RAD54L signaling axis.Respiratory research · 2026Article
- Epitranscriptomic control of cancer: the emerging roles of m⁵C and ac⁴C RNA modifications.Cell death discovery · 2026Review
- mBiology direct · 2026Review
- Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.Experimental hematology & oncology · 2026Review
- MIF-expressing tumor cells mediate immunotherapeutic resistance in esophageal squamous cell carcinoma.Theranostics · 2026Article
- Dynamic Evolution of the Tumor Immune Microenvironment in Malignant Tumors and Emerging Therapeutic Paradigms.MedComm · 2025Review
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Authors and funding
17 authors.
Funding
Abstract
Alterations in copy number are crucial genetic events in the development of esophageal squamous cell carcinoma (ESCC). Here, we show that Tocopherol alpha transfer protein-like (TTPAL) is highly amplified and frequently overexpressed in human ESCC. Using Ttpal-KO mouse mode, we demonstrate that TTPAL promotes ESCC cell proliferation and accelerates tumor development by driving cholesterol biosynthesis. Mechanistically, TTPAL upregulates a key transcription factor in cholesterol biosynthesis-sterol regulatory element-binding transcription factor (SREBP2) in ESCC cells. TTPAL interacts with the RNA methyltransferase NSUN2 and relieves the ubiquitination of NSUN2, protecting NSUN2 from proteasome-mediated degradation. In turn, NSUN2 catalyzes the m5C modification of SREBP2 mRNA, and then the m5C modified SREBP2 mRNA binds to the m5C reader protein-ALYREF to enhance its stability, thereby increasing SREBP2 expression. Moreover, we validate the efficacy of cholesterol biosynthesis inhibitor simvastatin in ESCC with high TTPAL expression. Overall, our results uncover a novel function of TTPAL in regulating SREBP2 expression, revealed a previously unknown TTPAL/NSUN2/SREBP2 pathway that promotes cholesterol biosynthesis in ESCC cells, and identified sensitively to cholesterol biosynthesis inhibitor simvastatin.
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