ArticleCancer letters2023
MUC1-C is necessary for SHP2 activation and BRAF inhibitor resistance in BRAF(V600E) mutant colorectal cancer.
Article in Cancer letters, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- A comprehensive overview of the molecular features and therapeutic targets in BRAFClinical and translational medicine · 2024Pooled it
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- M1C IS NECESSARY FOR DARAXONRASIB RESISTANCE OF NSCLC KRAS(G12C) MUTANT CELLS.bioRxiv : the preprint server for biology · 2026Article
- SHP2 as a pivotal modulator of the tumor microenvironment in gastrointestinal cancers: from mechanisms to targeted therapies.Journal of translational medicine · 2026Review
- Evolution of the MUC1 gene in eutherian mammals as an adaptation responsible for the increasing incidence of cancer in humans.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Targeting SHP2: Dual breakthroughs in colorectal cancer therapy-from signaling pathway modulation to immune microenvironment remodeling.World journal of gastrointestinal oncology · 2025Review
- Advances and challenges in drug repurposing in precision therapeutics of colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- Induced clustering of SHP2-depleted tumor cells in vascular islands restores sensitivity to MEK/ERK inhibition.The Journal of clinical investigation · 2025Article
- Navigating PROTACs in Cancer Therapy: Advancements, Challenges, and Future Horizons.Food science & nutrition · 2025Review
- Biomimetic Nano-delivery of Small-Molecule Piceatannol Modulates Tumor Stemness and Suppresses Colorectal Cancer Metastasis via Hippo/YAP1/SOX9 Signaling.Small (Weinheim an der Bergstrasse, Germany) · 2025Article
- Review
- PROTACs: Current and Future Potential as a Precision Medicine Strategy to Combat Cancer.Molecular cancer therapeutics · 2024Review
- MUC1-C Is a Common Driver of Acquired Osimertinib Resistance in NSCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2024Article
- MUC1-C is a target of salinomycin in inducing ferroptosis of cancer stem cells.Cell death discovery · 2024Article
- MUC1 and MUC16: critical for immune modulation in cancer therapeutics.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Colorectal cancers (CRCs) harboring the BRAF(V600E) mutation are associated with aggressive disease and resistance to BRAF inhibitors by feedback activation of the receptor tyrosine kinase (RTK)→RAS→MAPK pathway. The oncogenic MUC1-C protein promotes progression of colitis to CRC; whereas there is no known involvement of MUC1-C in BRAF(V600E) CRCs. The present work demonstrates that MUC1 expression is significantly upregulated in BRAF(V600E) vs wild-type CRCs. We show that BRAF(V600E) CRC cells are dependent on MUC1-C for proliferation and BRAF inhibitor (BRAFi) resistance. Mechanistically, MUC1-C integrates induction of MYC in driving cell cycle progression with activation of the SHP2 phosphotyrosine phosphatase, which enhances RTK-mediated RAS→ERK signaling. We demonstrate that targeting MUC1-C genetically and pharmacologically suppresses (i) activation of MYC, (ii) induction of the NOTCH1 stemness factor, and (iii) the capacity for self-renewal. We also show that MUC1-C associates with SHP2 and is required for SHP2 activation in driving BRAFi-induced feedback of ERK signaling. In this way, targeting MUC1-C in BRAFi-resistant BRAF(V600E) CRC tumors inhibits growth and sensitizes to BRAF inhibition. These findings demonstrate that MUC1-C is a target for the treatment of BRAF(V600E) CRCs and for reversing their resistance to BRAF inhibitors by suppressing the feedback MAPK pathway.
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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.