ArticleCancer gene therapy2013
Co-delivery of LETM1 and CTMP synergistically inhibits tumor growth in H-ras12V liver cancer model mice.
Article in Cancer gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Navigating liver cancer: Precision targeting for enhanced treatment outcomes.Drug delivery and translational research · 2025Review
- Overview of carboxyl‑terminal modulator protein 1 and its importance in various metabolic regulations (Review).Molecular medicine reports · 2024Review
- Roles of THEM4 in the Akt pathway: a double-edged sword.Journal of Zhejiang University. Science. B · 2024Review
- Mitochondrial Cristae Morphology Reflecting Metabolism, Superoxide Formation, Redox Homeostasis, and Pathology.Antioxidants & redox signaling · 2023Review
- Mitochondrial calcium exchange in physiology and disease.Physiological reviews · 2022Review
- Exosomal miR-183-5p Shuttled by M2 Polarized Tumor-Associated Macrophage Promotes the Development of Colon CancerFrontiers in oncology · 2021Article
- LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling.Frontiers in physiology · 2021Review
- Carboxyl-Terminal Modulator Protein Ameliorates Pathological Cardiac Hypertrophy by Suppressing the Protein Kinase B Signaling Pathway.Journal of the American Heart Association · 2018Article
- LETM1 overexpression is correlated with the clinical features and survival outcome of breast cancer.International journal of clinical and experimental pathology · 2015Article
- High expression of leucine zipper-EF-hand containing transmembrane protein 1 predicts poor prognosis in head and neck squamous cell carcinoma.BioMed research international · 2014Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
As hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, development of novel therapeutic approaches for HCC is urgently needed. Two different genes, LETM1 and CTMP, which target mitochondrial functions, were chosen and linked using 2A-peptide sequence. Successful self-cleavage of 2A-peptide induced synergistic antitumor effect in the liver of H-ras12V, the HCC model mice, by simultaneous activation of LETM1 (Leucine zipper/EF hand-containing transmembrane-1) and CTMP (carboxyl-terminal modulator protein). Overexpression of LETM1 and CTMP significantly reduced the incidence of tumorigenesis, which were confirmed by gross and microscopic observations. Morphological changes in mitochondria, such as swelling and loss of cristae, were significant, and the prolonged activation of defects in mitochondrial function led to mitochondria-mediated apoptosis. Furthermore, with CTMP as a direct binding partner of Akt1, and LETM1 as a binding partner of CTMP, LETM1-2A-CTMP downregulated the Akt1 pathway at both Ser473 and Thr308 sites of phosphorylation. Proliferation and angiogenesis, which are important in cancer prognosis, were reduced in tumor sites after introduction of LETM1-2A-CTMP. Taken together, the results indicate that introduction of the mitochondria-targeting genes, LETM1 and CTMP, and self-processing capacity of 2A-peptide sequence exerts an antitumor effect in liver of H-ras12V mice, suggesting its potential as a tool for gene therapy.
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