ArticleOncotarget2017
NFkB is essential for activin-induced colorectal cancer migration via upregulation of PI3K-MDM2 pathway.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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Who cites it
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 87 citations in OpenAlex.
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- Genetic Association betweenDisease markers · 2019Pooled it
- Glucocorticoid receptor-targeted liposomal delivery of wnt/β-catenin pathway inhibitor selectively induces efficient colorectal tumor regression.Drug delivery and translational research · 2026Article
- Elevated TNF-α level is correlated with NF-κB/p65 activation in patients with sporadic colorectal cancer.Molecular and clinical oncology · 2026Article
- The Association and Significance of MDM2 and NF-κB Protein Expression in Multiple Myeloma.Medicina (Kaunas, Lithuania) · 2025Article
- Deciphering the metabolic landscape of colorectal cancer through the lens of AhR-mediated intestinal inflammation.Discover oncology · 2025Review
- The bacterial microbiome and cancer: development, diagnosis, treatment, and future directions.Clinical and experimental medicine · 2024Review
- Mdm2 requires Sprouty4 to regulate focal adhesion formation and metastasis independent of p53.Nature communications · 2024Article
- Phytochemical Composition Antioxidant and Anti-Inflammatory Activity ofAntioxidants (Basel, Switzerland) · 2024Article
- Exploring the relationship between anastasis and mitochondrial ROS-mediated ferroptosis in metastatic chemoresistant cancers: a call for investigation.Frontiers in immunology · 2024Review
- Anastasis enhances metastasis and chemoresistance of colorectal cancer cells through upregulating cIAP2/NFκB signaling.Cell death & disease · 2023Article
- Review
- Promising Modulatory Effects of Cenicriviroc on the Progression of Mouse Colorectal Cancer through Inhibition of CCR2_CCL2 Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2023Article
- Thioredoxin domain-containing protein 9 protects cells against UV-B-provoked apoptosis via NF-κB/p65 activation in cutaneous squamous cell carcinoma.Oncology research · 2023Article
- Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers.Cancers · 2022Review
- Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas.BMC cancer · 2022Article
- The Role of Inflammatory Cytokines in the Pathogenesis of Colorectal Carcinoma-Recent Findings and Review.Biomedicines · 2022Review
- ERβ and Inflammation.Advances in experimental medicine and biology · 2022Article
- Single-Cell RNA Sequencing Reveals the Heterogeneity of Infiltrating Immune Cell Profiles in the Hepatic Cystic Echinococcosis Microenvironment.Infection and immunity · 2021Article
- Exploring the Inflammatory Pathogenesis of Colorectal Cancer.Diseases (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Colorectal cancer (CRC) remains a common and deadly cancer due to metastatic disease. Activin and TGFB (TGFβ) signaling are growth suppressive pathways that exert non-canonical pro-metastatic effects late in CRC carcinogenesis. We have recently shown that activin downregulates p21 via ubiquitination and degradation associated with enhanced cellular migration independent of SMADs. To investigate the mechanism of metastatic activin signaling, we examined activated NFkB signaling and activin ligand expression in CRC patient samples and found a strong correlation. We hypothesize that activation of the E3 ubiquitin ligase MDM2 by NFkB leads to p21 degradation in response to activin treatment. To dissect the link between activin and pro-carcinogenic NFkB signaling and downstream targets, we found that activin but not TGFB induced activation of NFkB leading to increased MDM2 ubiquitin ligase via PI3K. Further, overexpression of wild type p65 NFkB increased MDM2 expression while the NFkB inhibitors NEMO-binding domain (NBD) and Bay11-7082 blocked the activin-induced increase in MDM2. In conclusion, in colon cancer cell migration, activin utilizes NFkB to induce MDM2 activity leading to the degradation of p21 in a PI3K dependent mechanism. This provides new mechanistic knowledge linking activin and NFkB signaling in advanced colon cancer which is applicable to targeted therapeutic interventions.
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