ArticleJournal of cellular and molecular medicine2021
Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy.
Article in Journal of cellular and molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- Mitochondrial CaJournal of cellular physiology · 2025Review
- Serum Starvation Regulates Autophagy of Human Periodontal Ligament Cells Through Reactive Oxygen Species Mediated Adenosine Monophosphate-Activated Protein Kinase/Mechanistic Target of RAPAMYCIN Axis.International dental journal · 2025Article
- The dual role of autophagy in cancer stem cells: implications for tumor progression and therapy resistance.Journal of translational medicine · 2025Review
- Calcium signaling in mitochondrial intermembrane space.Biochemical Society transactions · 2024Review
- Role of Autophagy and AMPK in Cancer Stem Cells: Therapeutic Opportunities and Obstacles in Cancer.International journal of molecular sciences · 2024Review
- Roles of THEM4 in the Akt pathway: a double-edged sword.Journal of Zhejiang University. Science. B · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Aberrant LETM1 elevation dysregulates mitochondrial functions and energy metabolism and promotes lung metastasis in osteosarcoma.Genes & diseases · 2024Article
- Crosstalk between autophagy and CSCs: molecular mechanisms and translational implications.Cell death & disease · 2023Review
- The Concept of Cancer Stem Cells: Elaborating on ALDH1B1 as an Emerging Marker of Cancer Progression.Life (Basel, Switzerland) · 2023Review
- The Transcriptomic Mechanism of a Novel Autolysis Induced by a Recombinant Antibacterial Peptide from Chicken Expressed inMolecules (Basel, Switzerland) · 2022Article
- Autophagy: A Versatile Player in the Progression of Colorectal Cancer and Drug Resistance.Frontiers in oncology · 2022Review
- Review
- Suppression of LETM1 inhibits the proliferation and stemness of colorectal cancer cells through reactive oxygen species-induced autophagy.Journal of cellular and molecular medicine · 2021Article
- LETM1: A Single Entity With Diverse Impact on Mitochondrial Metabolism and Cellular Signaling.Frontiers in physiology · 2021Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Leucine zipper-EF-hand-containing transmembrane protein 1 (LETM1) is a mitochondrial inner membrane protein that is highly expressed in various cancers. Although LETM1 is known to be associated with poor prognosis in colorectal cancer (CRC), its roles in autophagic cell death in CRC have not been explored. In this study, we examined the mechanisms through which LETM1 mediates autophagy in CRC. Our results showed that LETM1 was highly expressed in CRC tissues and that down-regulation of LETM1 inhibited cell proliferation and induced S-phase arrest. LETM1 silencing also suppressed cancer stem cell-like properties and induced autophagy in CRC cells. Additionally, the autophagy inhibitor 3-methyladenine reversed the inhibitory effects of LETM1 silencing on proliferation and stemness, whereas the autophagy activator rapamycin had the opposite effects. Mechanistically, suppression of LETM1 increased the levels of reactive oxygen species (ROS) and mitochondrial ROS by regulation of SOD2, which in turn activated AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR), initiated autophagy, and inhibited proliferation and stemness. Our findings suggest that silencing LETM1 induced autophagy in CRC cells by triggering ROS-mediated AMPK/mTOR signalling, thus blocking CRC progression, which will enhance our understanding of the molecular mechanism of LETM1 in CRC.
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