ArticleJournal of experimental & clinical cancer research : CR2019
DTL promotes cancer progression by PDCD4 ubiquitin-dependent degradation.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 141 citations in OpenAlex.
- Salidroside Regulates DN Podocyte Injury Through the LncRNA ZEB1-AS1/miR-21-5p/PDCD4 Axis.Biochemical genetics · 2026Article
- OTUB2-mediated deubiquitination upregulates U2AF2 to promote colorectal cancer evasion of autophagy-ferroptosis.Cell death & disease · 2026Article
- Exosomal miR-373-3p Derived from Docetaxel-Resistant Lung Cancer Cells Targets PDCD4 to Promote Proliferation and Inhibit Apoptosis in Lung Cancer Cells.Biomedicines · 2026Article
- Article
- E2F8 Transcriptionally Activates DTL to Promote Endometrial Cancer Progression Via the MAPK Pathway.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- SKP2 in Cancer: From Molecular Regulation to Therapeutic Vulnerabilities and Translational Perspectives.Drug design, development and therapy · 2026Review
- Denticleless E3 Ubiquitin Protein Ligase Homolog as a Potential Biomarker for Adrenocortical Carcinoma Screening.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Molecular mechanisms and potential targeting strategies of ubiquitin‑proteasome system‑mediated PD‑1/PD‑L1 ubiquitination in tumor immune suppression (Review).Oncology reports · 2025Review
- Synergistic Anticancer Effects of Fermented Noni Extract Combined with 5-Fluorouracil, Doxorubicin, and Vincristine on A549, MCF-7, and SH-SY5Y Cell Models.Current issues in molecular biology · 2025Article
- Mutant NPM1 modulates PDCD4 ubiquitination degradation and facilitates leukemogenesis.iScience · 2025Article
- Identification of key candidate genes for ovarian cancer using integrated statistical and machine learning approaches.Briefings in bioinformatics · 2025Article
- LncRNA small nucleolar RNA host gene 1 (SNHG1) mediates acidic bile salt-induced EMT via the ULK1-Notch1 axis in Barrett's esophagus.Molecular biomedicine · 2025Article
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- UBE2T is a diagnostic and prognostic biomarker for endometrial cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- Construction of ubiquitination-related risk model for predicting prognosis in lung adenocarcinoma.Scientific reports · 2025Article
- An update on cancer stem cell survival pathways involved in chemoresistance in triple-negative breast cancer.Future oncology (London, England) · 2025Review
- Modification-specific Proteomic Analysis Reveals Cysteine S-Palmitoylation Involved in Esophageal Cancer Cell Radiation.ACS omega · 2025Article
- Comparative bioinformatics analysis of the Wnt pathway in breast cancer: Selection of novel biomarker panels associated with ER status.Open life sciences · 2025Article
- The Mechanism of Xuanyu Tongjing Decoction Regulating NOD/NFκB Pathway to Inhibit Ectopic Tissue Inflammation to Reduce Ovarian Damage in Rats with Ovarian Endometriosis.Drug design, development and therapy · 2025Article
- Evaluating the advancements in protein language models for encoding strategies in protein function prediction: a comprehensive review.Frontiers in bioengineering and biotechnology · 2025Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundUbiquitin E3 ligase CUL4A plays important oncogenic roles in the development of cancers. DTL, one of the CUL4-DDB1 associated factors (DCAFs), may involve in the process of cancer development. Programmed cell death 4 (PDCD4) is a tumor suppressor gene involved in cell apoptosis, transformation, invasion and tumor progression.
methodsAffinity-purification mass spectrometry was used to identify potential DTL interaction proteins. Co-immunoprecipitation (Co-IP) was performed to verify protein interaction between DTL and PDCD4. mRNA levels in cancer cells and tissues were detected by Quantitative real-time PCR. Lentivirus was used to establish stable overexpression and knocking down cell lines for DTL and PDCD4. Transwell and wound healing assays were used to determine migration ability of cancer cells. Matrigel assay was used to determine invasion ability of cancer cells. MTT and colony formation assays were used to evaluate proliferation of cancer cells.
resultsIn this study, programmed cell death 4 (PDCD4) was identified as a potential substrate of DTL. Co-IP and immunofluorescence assays further confirmed the interaction between DTL and PDCD4. Moreover, DTL overexpression decreased the protein level and accelerated the degradation rate of PDCD4. Through in vitro ubiquitination experiment, we proved that PDCD4 was degraded by DTL through ubiquitination. Clinically DTL was significantly up-regulated in cancer tissues than that in normal tissues. The survival curves showed that cancer patients with higher DTL expression owned lower survival rate. Functional experiments showed that DTL not only enhanced the proliferation and migration abilities of cancer cells, but also promoted the tumorigenesis in nude mice. Rescued experiment results demonstrated that silencing PDCD4 simultaneous with DTL recovered the phenotypes defect caused by DTL knocking down.
conclusionsOur results elucidated that DTL enhanced the motility and proliferation of cancer cells through degrading PDCD4 to promote the development of cancers.
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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.