ArticleOncogene2019
The protein secretion modulator TMED9 drives CNIH4/TGFα/GLI signaling opposing TMED3-WNT-TCF to promote colon cancer metastases.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 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
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- TMED family genes and their roles in human diseases.International journal of medical sciences · 2023Pooled it
- Chrysosplenetin-induced TMED3 aggregation triggers unfolded protein response in pancreatic cancer.EMBO molecular medicine · 2026Article
- IRE1-XBP1driven induction of TMED9 stabilizes ATF6 during ER stress to promote cell survival.Cellular & molecular biology letters · 2026Article
- Trafficking of the human NaProtein science : a publication of the Protein Society · 2026Article
- Glutamine-mediated crosstalk between M2 macrophages and tumor cells via the SLC38A5/FOXM1/CNIH4 axis promotes oral squamous cell carcinoma progression.Journal of translational medicine · 2026Article
- Bioinformatic Approach to Identify Positive PrognosticInternational journal of molecular sciences · 2025Article
- Article
- CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.Cellular & molecular biology letters · 2025Article
- TMED9: a potential therapeutic target and prognostic marker in glioma and its implications across pan-cancer contexts.Frontiers in immunology · 2025Article
- Deciphering the role of CNIH4 in pan-cancer landscapes and its significance in breast cancer progression.Frontiers in genetics · 2025Article
- Study of the role of transmembrane emp24 domain-containing protein 2 in oral squamous cell carcinoma.Journal of applied oral science : revista FOB · 2025Article
- Article
- Prognostic value and anti-tumor immunity role ofTranslational cancer research · 2024Article
- The Role of Cornichons in the Biogenesis and Functioning of Monovalent-Cation Transport Systems.Physiological research · 2024Review
- RHBDL4-triggered downregulation of COPII adaptor protein TMED7 suppresses TLR4-mediated inflammatory signaling.Nature communications · 2024Article
- Article
- Comprehensive analysis of clinical prognosis and biological significance of CNIH4 in cervical cancer.Cancer medicine · 2023Article
- Integrated analysis based on vesicle trafficking-related genes identifying CNIH4 as a novel therapeutic target for glioma.Cancer medicine · 2023Article
- Microphthalmia-Associated Transcription Factor: A Differentiation Marker in Uveal Melanoma.International journal of molecular sciences · 2023Article
- Trafficking protein TMED3 promotes esophageal squamous cell carcinoma.Biomedical journal · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
How cells in primary tumors initially become pro-metastatic is not understood. A previous genome-wide RNAi screen uncovered colon cancer metastatic suppressor and WNT promoting functions of TMED3, a member of the p24 ER-to-Golgi protein secretion family. Repression of canonical WNT signaling upon knockdown (kd) of TMED3 might thus be sufficient to drive metastases. However, searching for transcriptional influences on other family members here we find that TMED3 kd leads to enhanced TMED9, that TMED9 acts downstream of TMED3 and that TMED9 kd compromises metastasis. Importantly, TMED9 pro-metastatic function is linked to but distinct from the repression of TMED3-WNT-TCF signaling. Functional rescue of the migratory deficiency of TMED9 kd cells identifies TGFα as a mediator of TMED9 pro-metastatic activity. Moreover, TMED9 kd compromises the biogenesis, and thus function, of TGFα. Analyses in three colon cancer cell types highlight a TMED9-dependent gene set that includes CNIH4, a member of the CORNICHON family of TGFα exporters. Our data indicate that TGFA and CNIH4, which display predictive value for disease-free survival, promote colon cancer cell metastatic behavior, and suggest that TMED9 pro-metastatic function involves the modulation of the secretion of TGFα ligand. Finally, TMED9/TMED3 antagonism impacts WNT-TCF and GLI signaling, where TMED9 primacy over TMED3 leads to the establishment of a positive feedback loop together with CNIH4, TGFα, and GLI1 that enhances metastases. We propose that primary colon cancer cells can transition between two states characterized by secretion-transcription regulatory loops gated by TMED3 and TMED9 that modulate their metastatic proclivities.
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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.