ArticleThe Journal of biological chemistry2009
X-linked inhibitor of apoptosis protein and its E3 ligase activity promote transforming growth factor-{beta}-mediated nuclear factor-{kappa}B activation during breast cancer progression.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- E3 Ubiquitin Ligases in Breast Cancer Metastasis: A Systematic Review of Pathogenic Functions and Clinical Implications.Frontiers in oncology · 2021Pooled it
- TGF-β upregulates miR-181a expression to promote breast cancer metastasis.The Journal of clinical investigation · 2013Trial
- 5-Iodotubercidin inhibits epithelial to mesenchymal transition by inhibiting IKK/NFκB-dependent gene expression.The Journal of biological chemistry · 2026Article
- Dual signaling pathways of TGF-β superfamily cytokines in hepatocytes: balancing liver homeostasis and disease progression.Frontiers in pharmacology · 2025Review
- Advances and Challenges in Targeting TGF-β Isoforms for Therapeutic Intervention of Cancer: A Mechanism-Based Perspective.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Significance of combined TGF-β1 and survivin expression on the prognosis of patients with triple-negative breast cancer.Oncology letters · 2022Article
- Subcellular localization of X-linked inhibitor of apoptosis protein (XIAP) in cancer: Does that matter?BBA advances · 2022Review
- SLX4IP promotes RAP1 SUMOylation by PIAS1 to coordinate telomere maintenance through NF-κB and Notch signaling.Science signaling · 2021Article
- Review
- Ovarian Primary and Metastatic Tumors Suppressed by Survivin Knockout or a Novel Survivin Inhibitor.Molecular cancer therapeutics · 2019Article
- Targeting bone morphogenetic protein receptor 2 sensitizes lung cancer cells to TRAIL by increasing cytosolic Smac/DIABLO and the downregulation of X-linked inhibitor of apoptosis protein.Cell communication and signaling : CCS · 2019Article
- The lncRNA BORG facilitates the survival and chemoresistance of triple-negative breast cancers.Oncogene · 2019Article
- miR-203 inhibits ovarian tumor metastasis by targeting BIRC5 and attenuating the TGFβ pathway.Journal of experimental & clinical cancer research : CR · 2018Article
- Knockdown of survivin results in inhibition of epithelial to mesenchymal transition in retinal pigment epithelial cells by attenuating the TGFβ pathway.Biochemical and biophysical research communications · 2018Article
- Lentiviral CRISPR/Cas9 nickase vector mediated BIRC5 editing inhibits epithelial to mesenchymal transition in ovarian cancer cells.Oncotarget · 2017Article
- Inflammation and Epithelial-Mesenchymal Transition in Pancreatic Ductal Adenocarcinoma: Fighting Against Multiple Opponents.Cancer growth and metastasis · 2017Review
- Signaling Receptors for TGF-β Family Members.Cold Spring Harbor perspectives in biology · 2016Review
- LYTAK1, a TAK1 inhibitor, suppresses proliferation and epithelial‑mesenchymal transition in retinal pigment epithelium cells.Molecular medicine reports · 2016Article
- Inhibition of BMP and of TGFβ receptors downregulates expression of XIAP and TAK1 leading to lung cancer cell death.Molecular cancer · 2016Article
- X-linked inhibitor of apoptosis protein mediates tumor cell resistance to antibody-dependent cellular cytotoxicity.Cell death & disease · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The precise sequence of events that enable mammary tumorigenesis to convert transforming growth factor-beta (TGF-beta) from a tumor suppressor to a tumor promoter remains incompletely understood. We show here that X-linked inhibitor of apoptosis protein (xIAP) is essential for the ability of TGF-beta to stimulate nuclear factor-kappaB (NF-kappaB) in metastatic 4T1 breast cancer cells. Indeed whereas TGF-beta suppressed NF-kappaB activity in normal mammary epithelial cells, those engineered to overexpress xIAP demonstrated activation of NF-kappaB when stimulated with TGF-beta. Additionally up-regulated xIAP expression also potentiated the basal and TGF-beta-stimulated transcriptional activities of Smad2/3 and NF-kappaB. Mechanistically xIAP (i) interacted physically with the TGF-beta type I receptor, (ii) mediated the ubiquitination of TGF-beta-activated kinase 1 (TAK1), and (iii) facilitated the formation of complexes between TAK1-binding protein 1 (TAB1) and IkappaB kinase beta that enabled TGF-beta to activate p65/RelA and to induce the expression of prometastatic (i.e. cyclooxygenase-2 and plasminogen activator inhibitor-1) and prosurvival (i.e. survivin) genes. We further observed that inhibiting the E3 ubiquitin ligase function of xIAP or expressing a mutant ubiquitin protein (i.e. K63R-ubiquitin) was capable of blocking xIAP- and TGF-beta-mediated activation of NF-kappaB. Functionally xIAP deficiency dramatically reduced the coupling of TGF-beta to Smad2/3 in NMuMG cells as well as inhibited their expression of mesenchymal markers in response to TGF-beta. More importantly, xIAP deficiency also abrogated the formation of TAB1.IkappaB kinase beta complexes in 4T1 breast cancer cells, thereby diminishing their activation of NF-kappaB, their expression of prosurvival/metastatic genes, their invasion through synthetic basement membranes, and their growth in soft agar. Collectively our findings have defined a novel role for xIAP in mediating oncogenic signaling by TGF-beta in breast cancer cells.
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