ArticleCell death & disease2019
MKK3 sustains cell proliferation and survival through p38DELTA MAPK activation in colorectal cancer.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Low, plasma level‑informed native curcumin concentrations fail to induce cell death in human lung and colorectal cancer cells.Pharmaceutical biology · 2026Article
- Role of the ETV5/p38 Signaling Axis in Aggressive Thyroid Cancer Cells.Molecular cancer therapeutics · 2026Article
- Ubiquitin-specific protease 13 promotes colorectal cancer progression by stabilizing mitogen-activated protein kinase kinase 3.Molecular biomedicine · 2025Article
- CK2α Overexpression in Colorectal Cancer: Evidence for Sex- and Age-Linked Differences.Cancers · 2025Article
- scCOSMIX: A Mixed-Effects Framework for Differential Coexpression and Transcriptional Interactions Modeling in Single-Cell RNA-Seq.Statistics in medicine · 2025Article
- Natural products modulating MAPK for CRC treatment: a promising strategy.Frontiers in pharmacology · 2025Review
- CircSEC24B activates autophagy and induces chemoresistance of colorectal cancer via OTUB1-mediated deubiquitination of SRPX2.Cell death & disease · 2024Article
- Repurposed AT9283 triggers anti-tumoral effects by targeting MKK3 oncogenic functions in Colorectal Cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- Natural products targeting the MAPK-signaling pathway in cancer: overview.Journal of cancer research and clinical oncology · 2024Review
- MicroRNAs and MAPKs: Evidence of These Molecular Interactions in Alzheimer's Disease.International journal of molecular sciences · 2023Review
- Functional Roles of JNK and p38 MAPK Signaling in Nasopharyngeal Carcinoma.International journal of molecular sciences · 2022Review
- Review
- The p38 MAPK Components and Modulators as Biomarkers and Molecular Targets in Cancer.International journal of molecular sciences · 2021Review
- Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication.International journal of molecular sciences · 2021Article
- The miR-19b-3p-MAP2K3-STAT3 feedback loop regulates cell proliferation and invasion in esophageal squamous cell carcinoma.Molecular oncology · 2021Article
- A Special View of What Was Almost Forgotten: p38δ MAPK.Cancers · 2021Review
- High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients.Journal of translational medicine · 2020Article
- The p38 MAPK Signaling Activation in Colorectal Cancer upon Therapeutic Treatments.International journal of molecular sciences · 2020Review
- The c-Myc/miR-27b-3p/ATG10 regulatory axis regulates chemoresistance in colorectal cancer.Theranostics · 2020Article
- Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors worldwide and understanding its underlying molecular mechanisms is crucial for the development of therapeutic strategies. The mitogen-activated protein kinase-kinase 3 (MKK3) is a specific activator of p38 MAP kinases (p38 MAPKs), which contributes to the regulation of several cellular functions, such as proliferation, differentiation, apoptosis as well as response to drugs. At present, the exact MKK3/p38 MAPK pathway contribution in cancer is heavily debated because of its pleiotropic function. In this work, we retrospectively explored the prognostic and pathobiologic relevance of MKK3 in a cohort of CRC patients and assessed MKK3 molecular functions in a panel of CRC lines and colonocytes primary cultures. We found increased MKK3 levels in late-stage CRC patients which correlated with shorter overall survival. Herein, we report that the MKK3 targeting by inducible RNA interference univocally exerts antitumor effects in CRC lines but not in primary colonocytes. While MKK3 depletion per se affects growth and survival by induction of sustained autophagy and death in some CRC lines, it potentiates response to chemotherapeutic drug 5-fluorouracil (5-FU) in all of the tested CRC lines in vitro. Here, we demonstrate for the first time that in CRC the MKK3 specifically activates p38delta MAPK isoform to sustain prosurvival signaling and that such effect is exacerbated upon 5-FU challenge. Indeed, p38delta MAPK silencing recapitulates MKK3 depletion effects in CRC cells in vitro and in vivo. Overall, our data identified a molecular mechanism through which MKK3 supports proliferation and survival signaling in CRC, further supporting MKK3 as a novel and extremely attractive therapeutic target for the development of promising strategies for the management of CRC patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.