ArticleMolecular cancer2016
Inhibition of BMP and of TGFβ receptors downregulates expression of XIAP and TAK1 leading to lung cancer cell death.
Article in Molecular cancer, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 48 citations in OpenAlex.
- SNX8 regulates BMPR2-mediated SMAD5 proteostasis to drive epithelial-mesenchymal transition in hepatocellular carcinoma.Journal of translational medicine · 2026Article
- Bone morphogenetic protein receptor 2 signaling mediates mitochondrial CaCell communication and signaling : CCS · 2026Article
- Article
- Exploring Smad5: a review to pave the way for a deeper understanding of the pathobiology of common respiratory diseases.Molecular medicine (Cambridge, Mass.) · 2024Review
- BMP receptor 2 inhibition regulates mitochondrial bioenergetics to induce synergistic cell death with BCL-2 inhibitors in leukemia and NSLC cells.Research square · 2024Article
- BMP signaling in cancer stemness and differentiation.Cell regeneration (London, England) · 2023Review
- Transforming growth factor-β and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.Cell cycle (Georgetown, Tex.) · 2023Review
- Interleukin-6 and pulmonary hypertension: from physiopathology to therapy.Frontiers in immunology · 2023Review
- PPDPF promotes lung adenocarcinoma progression via inhibiting apoptosis and NK cell-mediated cytotoxicity through STAT3.Oncogene · 2022Article
- Ym155 localizes to the mitochondria leading to mitochondria dysfunction and activation of AMPK that inhibits BMP signaling in lung cancer cells.Scientific reports · 2022Article
- The role of miR-370 and miR-138 in the regulation of BMP2 suppressor gene expression in colorectal cancer: preliminary studies.Journal of cancer research and clinical oncology · 2022Article
- Bone morphogenetic protein inhibitors and mitochondria targeting agents synergistically induce apoptosis-inducing factor (AIF) caspase-independent cell death in lung cancer cells.Cell communication and signaling : CCS · 2022Article
- Bone morphogenetic protein signaling regulation of AMPK and PI3K in lung cancer cells and C. elegans.Cell & bioscience · 2022Article
- Bone morphogenetic protein receptor inhibitors suppress the growth of glioblastoma cells.Molecular and cellular biochemistry · 2022Article
- Two Modulators of Skeletal Development: BMPs and Proteoglycans.Journal of developmental biology · 2022Review
- Bone morphogenetic protein receptor 2 inhibition destabilizes microtubules promoting the activation of lysosomes and cell death of lung cancer cells.Cell communication and signaling : CCS · 2021Article
- Inhibiting roles of FOXA2 in liver cancer cell migration and invasion by transcriptionally suppressing microRNA-103a-3p and activating the GREM2/LATS2/YAP axis.Cytotechnology · 2021Article
- Bone Morphogenic Protein Signaling and Melanoma.Current treatment options in oncology · 2021Review
- XIAP's Profile in Human Cancer.Biomolecules · 2020Review
- Autocrine BMP4 Signaling Enhances Tumor Aggressiveness via Promoting Wnt/β-Catenin Signaling in IDH1-mutant Gliomas.Translational oncology · 2020Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBone morphogenetic proteins (BMP) are embryonic proteins that are part of the transforming growth factor (TGFβ) superfamily, which are aberrantly expressed in many carcinomas. Inhibition of BMP receptors with small molecule inhibitors decreases growth and induces death of lung cancer cells, which involves the downregulation of Id1 and Id3 by a Smad dependent mechanism. Developmentally, BMP and TGFβ signaling utilizes Smad-1/5 independent mechanisms to stabilize the expression of X-linked inhibitor of apoptosis protein (XIAP) and activate TGFβ activated kinase 1 (TAK1), which are known to be potent inhibitors of apoptosis. The role of BMP signaling in regulating XIAP and TAK1 in cancer cells is poorly understood. Furthermore, the interaction between the BMP and TGFβ signaling cascades in regulating the activation of TAK1 in cancer cells has not been elucidated.
methodsFeedback regulation between the BMP and TGFβ signaling pathways and their regulation of XIAP, TAK1, and Id1 were examined in lung cancer cells utilizing siRNA and inhibitors targeting BMP type I receptors, inhibitors of BMP and TGFβ type I receptors, and an inhibitor of BMP and TGFβ type I and type II receptors.
resultsWe show that upon inhibition of BMP signaling in lung cancer cells, the TGFβ signaling cascade is activated. Both the BMP and TGFβ pathways activate TAK1, which then increases the expression of Id1. Inhibition of TGFβ signaling increased Id1 expression except when BMP signaling is suppressed, which then causes a dose-related decrease in the expression of Id1. Inhibition of both BMP and TGFβ signaling enhances the downregulation of TAK1. Our data also suggests that the blockade of the BMP type II receptor enhances the downregulation XIAP, which is important in decreasing the activity of TAK1. Knockdown studies demonstrate that both XIAP and TAK1 regulate the survival of lung cancer cells.
conclusionsThis paper highlights that targeting the BMP and TGFβ type I and type II receptors causes a downregulation of XIAP, TAK1, and Id1 leading to cell death of lung cancer cells. Small molecule inhibitors targeting the BMP and TGFβ receptors represents a potential novel means to treat cancer patients.
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