ArticleTranslational oncology2020
RUNX2/CBFB modulates the response to MEK inhibitors through activation of receptor tyrosine kinases in KRAS-mutant colorectal cancer.
Article in Translational oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Disulfidptosis mechanisms and therapeutic implications in cancer metabolic reprogramming and future perspectives.Discover oncology · 2025Review
- RUNX2 inhibition disrupts a PAX3::FOXO1-RUNX2 feed-forward loop and dismantles oncogenic gene programs in fusion-positive rhabdomyosarcoma.bioRxiv : the preprint server for biology · 2025Article
- Identification biomarkers and therapeutic targets of disulfidptosis-related in rheumatoid arthritis via bioinformatics, molecular dynamics simulation, and experimental validation.Scientific reports · 2025Article
- E3 Ubiquitination Ligase MYLIP Mediates the NKRF/SLC25A34 Axis to Suppress Malignant Progression in Colorectal Cancer.Digestive diseases and sciences · 2025Article
- CBF-Beta Mitigates PI3K-Alpha-Specific Inhibitor Killing through PIM1 in PIK3CA-Mutant Gastric Cancer.Molecular cancer research : MCR · 2023Article
- A bioinformatics approach to identify a disulfidptosis-related gene signature for prognostic implication in colon adenocarcinoma.Scientific reports · 2023Article
- Identification of Moesin (MSN) as a Potential Therapeutic Target for Colorectal Cancer via the β-Catenin-RUNX2 Axis.International journal of molecular sciences · 2023Article
- Identification and validation of transcription factor-driven enhancers of genes related to lipid metabolism in metastatic oral squamous cell carcinomas.BMC oral health · 2022Article
- Oncoprotein-specific molecular interaction maps (SigMaps) for cancer network analyses.Nature biotechnology · 2021Article
Corrections and comments
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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
Intrinsic and acquired resistances are major hurdles preventing the effective use of MEK inhibitors for treatment of colorectal cancer (CRC). Some 35-45% of colorectal cancers are KRAS-mutant and their treatment remains challenging as these cancers are refractory to MEK inhibitor treatment, because of feedback activation of receptor tyrosine kinases (RTKs). We reported previously that loss of ERN1 sensitizes a subset of KRAS-mutant colon cancer cells to MEK inhibition. Here we show that the loss of RUNX2 or its cofactor CBFB can confer MEK inhibitor resistance in CRC cells. Mechanistically, we find that cells with genetically ablated RUNX2 or CBFB activate multiple RTKs, which coincides with high SHP2 phosphatase activity, a phosphatase that relays signals from the cell membrane to downstream pathways governing growth and proliferation. Moreover, we show that high activity of SHP2 is causal to loss of RUNX2-induced MEK inhibitor resistance, as a small molecule SHP2 inhibitor reinstates sensitivity to MEK inhibitor in RUNX2 knockout cells. Our results reveal an unexpected role for loss of RUNX2/CBFB in regulating RTK activity in colon cancer, resulting in reduced sensitivity to MEK inhibitors.
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Registered trials
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.