ArticleJournal of experimental & clinical cancer research : CR2014
SPOP suppresses tumorigenesis by regulating Hedgehog/Gli2 signaling pathway in gastric cancer.
Article in Journal of experimental & clinical cancer research : CR, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- The association of speckle-type POZ protein with lymph node metastasis and prognosis in cancer patients: A meta-analysis.Medicine · 2019Pooled it
- Review
- Molecular insights for the tumor suppressor role of SPOP in prostate cancer.Biochimica et biophysica acta. Reviews on cancer · 2026Review
- Reduced YTHDF2 inhibits PD-L1 expression by stabilizing mCell death & disease · 2026Article
- hnRNPA3 promotes the proliferation of hepatocellular carcinoma cells by stabilizing GLI2 proteins and activating Hedgehog pathway.Hepatology international · 2026Article
- O-GlcNAcylation of SPOP regulates colorectal cancer progression and ferroptosis by mediating β-catenin degradation.Cell death discovery · 2025Article
- Cul3 substrate adaptor SPOP targets Nup153 for degradation.Molecular biology of the cell · 2025Article
- Challenges and opportunities for the diverse substrates of SPOP E3 ubiquitin ligase in cancer.Theranostics · 2025Review
- Article
- TMEM160 promotes tumor immune evasion and radiotherapy resistance via PD-L1 binding in colorectal cancer.Cell communication and signaling : CCS · 2024Article
- Zinc Finger Proteins in the War on Gastric Cancer: Molecular Mechanism and Clinical Potential.Cells · 2023Review
- Interrogating bromodomain inhibitor resistance in KMT2A-rearranged leukemia through combinatorial CRISPR screens.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Frontiers in cell and developmental biology · 2023Review
- UPS: Opportunities and challenges for gastric cancer treatment.Frontiers in oncology · 2023Review
- Speckle-type POZ protein could play a potential inhibitory role in human renal cell carcinoma.BMC cancer · 2022Article
- Review
- rs2671655 single nucleotide polymorphism modulates the risk for gastric cancer in Helicobacter pylori-infected individuals: a genome-wide association study in the Korean population.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2022Article
- A Synopsis of Signaling Crosstalk of Pericytes and Endothelial Cells in Salivary Gland.Dentistry journal · 2021Review
- Clinicopathological and prognostic significance of speckle-type POZ protein in cancers: a systematic review and meta-analysis.Cancer cell international · 2021Review
- The Role of Smoothened-Dependent and -Independent Hedgehog Signaling Pathway in Tumorigenesis.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including gastric cancer. Speckle-type POZ protein, SPOP, is an E3 ubiquitin ligase adaptor, and it is found to inhibit oncogenic signaling. However, the molecular mechanisms are largely unknown.
methodsIn this study, we characterized the expression of SPOP in 88 pairs of gastric cancer tissues and adjacent tissues by immunohistochemical staining and Western blotting. The relationship between SPOP expression and clinical pathologic factors was analyzed. Transfected gastric cancer cell lines were used in cell viability, wound healing and colony formation assays. The interaction of SPOP with Gli2 and other related apoptotic proteins was assessed by immunoprecipitation, Western blotting, real-time PCR and dual luciferase reporter assays. Intracellular interaction of SPOP and Gli2 was visualized by immunofluorescent staining in gastric cancer cells.
resultsImmunohistochemical staining of SPOP can be detected in gastric cancer tissues but much less than adjacent gastric tissues (P < 0.01). High SPOP expression is negatively correlated with lymph node metastasis, poor histological differentiation, and tumor malignancy according to TNM staging. In vitro experiments revealed that over-expression of SPOP prevented tumor cells from proliferation, migration and colony formation in gastric cancer cell lines. Likewise, repression of SPOP promoted cell viability, migration, proliferation, and attenuated apoptosis. Mechanistic studies revealed that increasing SPOP accelerated Gli2 degradation but regardless of Gli2 synthesis. Furthermore, cytoplasmic Gli2 decreased markedly along with the abundant expression of SPOP in MKN45 cells.
conclusionsOur findings indicate that SPOP plays critical roles in suppressing gastric tumorigenesis through inhibiting Hh/Gli2 signaling pathway. It may provide an alternative strategy for developing therapeutic agents of gastric cancer in future.
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