ArticleGastroenterology2013
SPDEF functions as a colorectal tumor suppressor by inhibiting β-catenin activity.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 54 citations in OpenAlex.
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- Single nuclear RNA sequencing of terminal ileum in patients with cirrhosis demonstrates multi-faceted alterations in the intestinal barrier.Cell & bioscience · 2024Article
- Integrative analysis of spatial and single-cell transcriptome data from human pancreatic cancer reveals an intermediate cancer cell population associated with poor prognosis.Genome medicine · 2024Article
- ETV7 promotes colorectal cancer progression through upregulation of IFIT3.Functional & integrative genomics · 2024Article
- Clustering malignant cell states using universally variable genes.Briefings in bioinformatics · 2023Article
- Recapitulation of patient-specific 3D chromatin conformation using machine learning.Cell reports methods · 2023Article
- Poly(ADP-ribose) Polyremase-1 (PARP-1) Inhibition: A Promising Therapeutic Strategy for ETS-Expressing Tumours.International journal of molecular sciences · 2023Review
- SPDEF enhances cancer stem cell-like properties and tumorigenesis through directly promoting GALNT7 transcription in luminal breast cancer.Cell death & disease · 2023Article
- SPINKs in Tumors: Potential Therapeutic Targets.Frontiers in oncology · 2022Review
- Construction of an Epithelial-Mesenchymal Transition-Related Model for Clear Cell Renal Cell Carcinoma Prognosis Prediction.Disease markers · 2022Article
- SPDEF suppresses head and neck squamous cell carcinoma progression by transcriptionally activating NR4A1.International journal of oral science · 2021Article
- A CRISPR/Cas9-EngineeredCancer discovery · 2021Article
- Atonal bHLH transcription factor 1 is an important factor for maintaining the balance of cell proliferation and differentiation in tumorigenesis.Oncology letters · 2020Review
- Glutamate Ionotropic Receptor Kainate Type Subunit 3 (GRIK3) promotes epithelial-mesenchymal transition in breast cancer cells by regulating SPDEF/CDH1 signaling.Molecular carcinogenesis · 2019Article
- AR-PDEF pathway promotes tumour proliferation and upregulates MYC-mediated gene transcription by promoting MAD1 degradation in ER-negative breast cancer.Molecular cancer · 2018Article
- ELF3, ELF5, EHF and SPDEF Transcription Factors in Tissue Homeostasis and Cancer.Molecules (Basel, Switzerland) · 2018Review
- Article
- Role of ADAM10 in intestinal crypt homeostasis and tumorigenesis.Biochimica et biophysica acta. Molecular cell research · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsExpression of the SAM pointed domain containing ETS transcription factor (SPDEF or prostate-derived ETS factor) is regulated by Atoh1 and is required for the differentiation of goblet and Paneth cells. SPDEF has been reported to suppress the development of breast, prostate, and colon tumors. We analyzed levels of SPDEF in colorectal tumor samples from patients and its tumor-suppressive functions in mouse models of colorectal cancer (CRC).
methodsWe analyzed levels of SPDEF messenger RNA and protein in more than 500 human CRC samples and more than 80 nontumor controls. Spdef(-/-)and wild-type mice (controls) were either bred with Apc(Min/+) mice, or given azoxymethane (AOM) and dextran sodium sulfate (DSS), or 1,2-dimethylhydrazine and DSS, to induce colorectal tumors. Expression of Spdef also was induced transiently by administration of tetracycline to Spdef(dox-intestine) mice with established tumors, induced by the combination of AOM and DSS or by breeding with Apc(Min/+) mice. Colon tissues were collected and analyzed for tumor number, size, grade, and for cell proliferation and apoptosis. We also analyzed the effects of SPDEF expression in HCT116 and SW480 human CRC cells.
resultsIn colorectal tumors from patients, loss of SPDEF was observed in approximately 85% of tumors and correlated with progression from normal tissue, to adenoma, to adenocarcinoma. Spdef(-/-); Apc(Min/+) mice developed approximately 3-fold more colon tumors than Spdef(+/+); Apc(Min/+) mice. Likewise, Spdef(-/-) mice developed approximately 3-fold more colon tumors than Spdef(+/+) mice after administration of AOM and DSS. After administration of 1,2-dimethylhydrazine and DSS, invasive carcinomas were observed exclusively in Spdef(-/-) mice. Conversely, expression of SPDEF was sufficient to promote cell-cycle exit in cells of established adenomas from Spdef(dox-intestine); Apc(Min/+) mice and in Spdef(dox-intestine) mice after administration of AOM + DSS. SPDEF inhibited the expression of β-catenin-target genes in mouse colon tumors, and interacted with β-catenin to block its transcriptional activity in CRC cell lines, resulting in lower levels of cyclin D1 and c-MYC.
conclusionsSPDEF is a colon tumor suppressor and a candidate therapeutic target for colon adenomas and adenocarcinoma.
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Registered trials
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