ArticleCell communication and signaling : CCS2019
Induction of LEF1 by MYC activates the WNT pathway and maintains cell proliferation.
Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 91 citations in OpenAlex.
- The Impact of Targeting TRAF2 and NCK-Interacting Protein Kinase on Antitumor Effect and Tumor Immune Environment in c-MYC-High SCLC.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- Nap1L4a Cooperates with Scl/Klf1 to Recruit H2A.Z in Mediating Interactions Among Cis-Regulatory Elements and Transcription Required for Primitive Erythropoiesis in Zebrafish.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Multi-Target lncRNA-miRNA-mRNA TRIAD in Pancreatic Cancer Diagnosis and Therapy.International journal of molecular sciences · 2026Review
- Nucleolus as a cornerstone linking proliferation and metabolism to cellular responses to stress: involvement of transcription factors MYC and p53.Frontiers in molecular biosciences · 2026Review
- African spiny mice show resistance to DMBA/TPA-induced squamous carcinogenesis with distinct benign tumor profile.Protein & cell · 2025Article
- The miR-34/449 clusters regulate the differentiation of ciliated cells in the oviduct via the Wnt/β-catenin signaling pathway.Cell & bioscience · 2025Article
- Review
- ELTD1 inhibits differentiation of hemogenic endothelium progenitors from human embryonic stem cells through the HPIP-Wnt pathway.Experimental & molecular medicine · 2025Article
- Emerging pathological diagnostic strategies for solid pseudopapillary neoplasm of the pancreas: insights from omics and innovative techniques.The journal of pathology. Clinical research · 2025Review
- Transcriptome and Functional Comparison of Primary and Immortalized Endothelial Cells of the Human Choroid Plexus at the Blood-Cerebrospinal Fluid Barrier.International journal of molecular sciences · 2025Article
- Clinical Significance of Acyl-CoA Dehydrogenase Short Chain and Its Anti-tumor Role in Hepatocellular Carcinoma by Inhibiting Canonical Wnt/β-Catenin Pathway.Digestive diseases and sciences · 2025Article
- Regulatory role of PPAR in colorectal cancer.Cell death discovery · 2025Review
- Single-Cell RNA Sequencing Reveals LEF1 as a Prognostic Biomarker for Poor Outcomes in Oxaliplatin-Resistant Colorectal Cancer.Human mutation · 2025Article
- Small molecule valproic acid enhances ventral patterning of human neural tube organoids by regulating Wnt and Shh signalling.Cell proliferation · 2025Article
- Validation of quercetin in the treatment of colon cancer with diabetes via network pharmacology, molecular dynamics simulations, and in vitro experiments.Molecular diversity · 2024Article
- Knockouts ofiScience · 2024Article
- The Interplay among Wnt/β-catenin Family Members in Colorectal Adenomas and Surrounding Tissues.Biomedicines · 2024Article
- Phosphorylation of USP27X by PIM2 promotes glycolysis and breast cancer progression via deubiquitylation of MYC.Oncogene · 2024Article
- Enhanced bacterial cancer therapy delivering therapeutic RNA interference of c-Myc.Cell & bioscience · 2024Article
- Repurposing of US-FDA-approved drugs as negative modulators of ubiquitin specific protease-7 (USP7).Heliyon · 2024Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundWhile regulated WNT activity is required for normal development and stem cell maintenance, mutations that lead to constitutive activation of the WNT pathway cause cellular transformation and drive colorectal cancer. Activation of the WNT pathway ultimately leads to the nuclear translocation of β-catenin which, in complex with TCF/LEF factors, promotes the transcription of genes necessary for growth. The proto-oncogene MYC is one of the most critical genes activated downstream the WNT pathway in colon cancer. Here, we investigate the converse regulation of the WNT pathway by MYC.
methodsWe performed RNA-seq analyses to identify genes regulated in cells expressing MYC. We validated the regulation of genes in the WNT pathway including LEF1 by MYC using RT-qPCR, Western blotting, and ChIP-seq. We investigated the importance of LEF1 for the viability of MYC-expressing cells in in fibroblasts, epithelial cells, and colon cells. Bioinformatic analyses were utilized to define the expression of MYC-regulated genes in human colon cancer and metabolomics analyses were used to identify pathways regulated by LEF1 in MYC expressing cells.
resultsMYC regulates the levels of numerous WNT-related genes, including the β-catenin co-transcription factor LEF1. MYC activates the transcription of LEF1 and is required for LEF1 expression in colon cancer cells and in primary colonic cells transformed by APC loss of function, a common mutation in colon cancer patients. LEF1 caused the retention of β-catenin in the nucleus, leading to the activation of the WNT pathway in MYC-expressing cells. Consequently, MYC-expressing cells were sensitive to LEF1 inhibition. Moreover, we describe two examples of genes induced in MYC-expressing cells that require LEF1 activity: the peroxisome proliferator activated receptor delta (PPARδ) and the Acyl CoA dehydrogenase 9 (ACAD9).
conclusionsWe demonstrated that MYC is a transcriptional regulator of LEF1 in colonic cells. Our work proposes a novel pathway by which MYC regulates proliferation through activating LEF1 expression which in turn activates the WNT pathway.
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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.