ArticleFrontiers in oncology2022
Non-apoptotic activity of the mitochondrial protein SMAC/Diablo in lung cancer: Novel target to disrupt survival, inflammation, and immunosuppression.
Article in Frontiers in oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Beyond Infection: Mitochondrial Reprogramming and Immunometabolic Adaptation inDiseases (Basel, Switzerland) · 2026Article
- The second mitochondrial activator of caspases (SMAC) regulates growth, inflammation and mitochondrial integrity in cancer cells.Cell death and differentiation · 2026Article
- Aptamer-mediated targeting of CXCR3-B in acute lymphoblastic leukemia nalm-6 cells: an in silico and in vitro study.Molecular biology reports · 2026Article
- Cracking the shield: oncolytic viruses versus the tumor-immune fortress.Cancer cell international · 2026Review
- Survivin/BIRC5-derived peptide disrupts survivin dimerization and cell division and induces multifaceted anti-cancer effects.Molecular therapy. Oncology · 2026Article
- SMAC/DIABLO: A Guardian Angel in Boosting Anticancer Drug-Induced Apoptosis.Current molecular medicine · 2026Review
- Iridoids as Multi-target Neuroprotective Agents for Ischemic Stroke: Mechanisms and Therapeutic Potential.Mini reviews in medicinal chemistry · 2026Review
- Targeting Mitochondrial Dysfunction and Reactive Oxygen Species for Neurodegenerative Disease Treatment.International journal of molecular sciences · 2024Review
- 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
- Isorhamnetin Regulates Programmed Death Ligand-1 Expression by Suppressing the EGFR-STAT3 Signaling Pathway in Canine Mammary Tumors.International journal of molecular sciences · 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
- Apoptotic proteins with non-apoptotic activity: expression and function in cancer.Apoptosis : an international journal on programmed cell death · 2023Review
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Authors and funding
4 authors.
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Abstract
Mitochondrial SMAC/Diablo induces apoptosis by binding the inhibitor of apoptosis proteins (IAPs), thereby activating caspases and, subsequently, apoptosis. Previously, we found that despite its pro-apoptotic activity, SMAC/Diablo is overexpressed in cancer, and demonstrated that in cancer it possesses new essential and non-apoptotic functions that are associated with regulating phospholipid synthesis including modulating mitochondrial phosphatidylserine decarboxylase activity. Here, we demonstrate additional functions for SMAC/Diablo associated with inflammation and immunity. CRISPR/Cas9 SMAC/Diablo-depleted A549 lung cancer cells displayed inhibited cell proliferation and migration. Proteomics analysis of these cells revealed altered expression of proteins associated with lipids synthesis and signaling, vesicular transport and trafficking, metabolism, epigenetics, the extracellular matrix, cell signaling, and neutrophil-mediated immunity. SMAC-KO A549 cell-showed inhibited tumor growth and proliferation and activated apoptosis. The small SMAC-depleted "tumor" showed a morphology of alveoli-like structures, reversed epithelial-mesenchymal transition, and altered tumor microenvironment. The SMAC-lacking tumor showed reduced expression of inflammation-related proteins such as NF-kB and TNF-α, and of the PD-L1, associated with immune system suppression. These results suggest that SMAC is involved in multiple processes that are essential for tumor growth and progression. Thus, targeting SMAC's non-canonical function is a potential strategy to treat cancer.
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