ArticleNature communications2024
The microprotein HDSP promotes gastric cancer progression through activating the MECOM-SPINK1-EGFR signaling axis.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed.
- Micropeptide colorectal neoplasia differentially expressed (CRNDE) 84aa encoded by CRNDE elicits a T-cell immune response to breast cancer.Translational cancer research · 2026Article
- Microproteins in Human Physiology and Pathology.Biochemistry · 2026Review
- Long non-coding RNA LOC101926915-encoded micropeptide carboplatin-induced upregulation factor confers carboplatin resistance in ovarian cancer.CytoJournal · 2026Article
- HOXA9 drives lymphatic metastasis by activating the c-MYC-glycolysis-lactate axis in gastric cancer.Journal of translational medicine · 2025Article
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- CRISPR-Cas9 screening reveals microproteins regulating adipocyte proliferation and lipid metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Small open reading frame-encoded microproteins in cancer: identification, biological functions and clinical significance.Molecular cancer · 2025Review
- Micropeptides Encoded by Noncoding RNAs: Biological Functions and Roles in Diseases.Research (Washington, D.C.) · 2025Review
- Implication of protein post translational modifications in gastric cancer.Frontiers in cell and developmental biology · 2025Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
The presence of noncanonical open reading frames within lncRNAs (long non-coding RNAs) suggests their potential for translation, yielding various functional peptides or proteins. However, the existence and specific roles of these products in gastric cancer remain largely unclear. Here we identify the HOXA10-HOXA9-derived small protein (HDSP) in gastric cancer through comprehensive analysis and experimental validation, including mass spectrometry and western blotting. HDSP exhibits high expression and oncogenic roles in gastric cancer. Mechanistically, HDSP blocks TRIM25-mediated ubiquitination and degradation by interacting with MECOM, leading to MECOM accumulation and enhanced SPINK1 transcription-a gene promoting cancer via the EGFR signaling pathway. Furthermore, MECOM fosters HOXA10-HOXA9 transcription, establishing a feedback loop activating SPINK1-EGFR signaling. HDSP knockdown inhibits tumor growth in a PDX (patient-derived xenograft) model, and infusion of an artificially synthesized HDSP peptide as a neoantigen enhances immune cell-mediated anti-tumor efficacy against gastric cancer in vitro and in vivo. These findings propose HDSP as a potential therapeutic target or neoantigen candidate for gastric cancer treatment.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.