ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
A New Role for the Mitochondrial Pro-apoptotic Protein SMAC/Diablo in Phospholipid Synthesis Associated with Tumorigenesis.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Intelligent plant exosomes synergize miRNAs and cisplatin for spatiotemporally precise multimodal treatment for TNBC with high safety.Bioactive materials · 2026Article
- The second mitochondrial activator of caspases (SMAC) regulates growth, inflammation and mitochondrial integrity in cancer cells.Cell death and differentiation · 2026Article
- Assessment of the Novel rVSV-PD-1-4-1BBL Oncolytic Activity on Mouse and Human Cancer Cell Lines.Biomedicines · 2026Article
- Survivin/BIRC5-derived peptide disrupts survivin dimerization and cell division and induces multifaceted anti-cancer effects.Molecular therapy. Oncology · 2026Article
- SPG7-Mediated Regulation of mPTP and Mitochondrial Flickering in COPD: A Bioinformatics-Based Prediction of Mechanistic Framework.International journal of chronic obstructive pulmonary disease · 2026Article
- Proteome Microarray-Guided Global View: Multiple Pharmacological Targets of Icariin.Drug design, development and therapy · 2026Article
- Effects of Resveratrol on Nonmelanoma Skin Cancer (NMSC): A Comprehensive Review.Food science & nutrition · 2024Review
- DNA-methylation variability in normal mucosa: a field cancerization marker in patients with adenomatous polyps.Journal of the National Cancer Institute · 2024Article
- Interaction of SMAC with a survivin-derived peptide alters essential cancer hallmarks: Tumor growth, inflammation, and immunosuppression.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Two-Dimensional Polyacrylamide Gel Electrophoresis Coupled with Nanoliquid Chromatography-Tandem Mass Spectrometry-Based Identification of Differentially Expressed Proteins and Tumorigenic Pathways in the MCF7 Breast Cancer Cell Line Transfected for Jumping Translocation Breakpoint Protein Overexpression.International journal of molecular sciences · 2023Article
- The Current Status of the Liver Liquid Biopsy in MASH Related HCC: Overview and Future Directions.Biomolecules · 2023Review
- Apoptotic proteins with non-apoptotic activity: expression and function in cancer.Apoptosis : an international journal on programmed cell death · 2023Review
- Non-apoptotic activity of the mitochondrial protein SMAC/Diablo in lung cancer: Novel target to disrupt survival, inflammation, and immunosuppression.Frontiers in oncology · 2022Article
- ILP-2: A New Bane and Therapeutic Target for Human Cancers.Frontiers in oncology · 2022Review
- SMAC/Diablo controls proliferation of cancer cells by regulating phosphatidylethanolamine synthesis.Molecular oncology · 2021Article
- Exogenous Introduction of Initiator and Executioner Caspases Results in Different Apoptotic Outcomes.JACS Au · 2021Article
- Apoptosis - Fueling the oncogenic fire.The FEBS journal · 2021Review
- VDAC1 Silencing in Cancer Cells Leads to Metabolic Reprogramming That Modulates Tumor Microenvironment.Cancers · 2021Article
- Exhaled breath condensates from healthy children induce cell death ofPostepy dermatologii i alergologii · 2021Article
- Coexpression of Smac/DIABLO and Estrogen Receptor in breast cancer.Cancer biomarkers : section A of Disease markers · 2021Article
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The mitochondrial pro-apoptotic protein SMAC/Diablo participates in apoptosis by negatively regulating IAPs and activating caspases, thus encouraging apoptosis. Unexpectedly, we found that SMAC/Diablo is overexpressed in cancer. This paradox was addressed here by silencing SMAC/Diablo expression using specific siRNA (si-hSMAC). In cancer cell lines and subcutaneous lung cancer xenografts in mice, such silencing reduced cell and tumor growth. Immunohistochemistry and electron microscopy of the si-hSMAC-treated residual tumor demonstrated morphological changes, including cell differentiation and reorganization into glandular/alveoli-like structures and elimination of lamellar bodies, surfactant-producing organs. Next-generation sequencing of non-targeted or si-hSMAC-treated tumors revealed altered expression of genes associated with the cellular membrane and extracellular matrix, of genes found in the ER and Golgi lumen and in exosomal networks, of genes involved in lipid metabolism, and of lipid, metabolite, and ion transporters. SMAC/Diablo silencing decreased the levels of phospholipids, including phosphatidylcholine. These findings suggest that SMAC/Diablo possesses additional non-apoptotic functions related to regulating lipid synthesis essential for cancer growth and development and that this may explain SMAC/Diablo overexpression in cancer. The new lipid synthesis-related function of the pro-apoptotic protein SMAC/Diablo in cancer cells makes SMAC/Diablo a promising therapeutic target.
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