ArticleBritish journal of cancer2015
TIM-4 promotes the growth of non-small-cell lung cancer in a RGD motif-dependent manner.
Article in British journal of cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 41 citations in OpenAlex.
- Restricting efferocytosis pathway to CD91 via phosphatidylserine-targeting chimeric protein augments antitumor immune responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Programmed cell death in lung cancer: mechanisms, immune responses, and therapeutics.Apoptosis : an international journal on programmed cell death · 2026Review
- Infiltration of TIM4-positive intratumoral macrophages serves as an adverse prognostic factor in breast cancer.Breast cancer (Tokyo, Japan) · 2026Article
- Machine learning-driven exosome-mimetic lipid nanoparticles for tumor-specific targeting.Nano convergence · 2026Article
- A Pan-Cancer Study of Tumour-Associated Efferocytosis Core Genes and Preliminary Exploration of TIMD4 in Renal Cell Carcinoma.Journal of cellular and molecular medicine · 2025Article
- Targeting Frequent Efferocytosis in Tumor Microenvironment is a New Direction for Cancer Treatment.Small science · 2025Review
- Directed protein engineering identifies a human TIM-4 blocking antibody that enhances anti-tumor response to checkpoint inhibition in murine colon carcinoma.Antibody therapeutics · 2024Article
- TIM-4 increases the proportion of CD4Cancer medicine · 2024Article
- Gene expression prognostic of early relapse risk in low-risk B-cell acute lymphoblastic leukaemia in children.EJHaem · 2024Article
- Article
- TIM-4 orchestrates mitochondrial homeostasis to promote lung cancer progression via ANXA2/PI3K/AKT/OPA1 axis.Cell death & disease · 2023Article
- Function and characteristics of TIM‑4 in immune regulation and disease (Review).International journal of molecular medicine · 2023Review
- Serum immune mediators as novel predictors of response to anti-PD-1/PD-L1 therapy in non-small cell lung cancer patients with high tissue-PD-L1 expression.Frontiers in immunology · 2023Article
- Drugging the efferocytosis process: concepts and opportunities.Nature reviews. Drug discovery · 2022Review
- The role of phosphatidylserine on the membrane in immunity and blood coagulation.Biomarker research · 2022Review
- N-Glycosylation at Asn291 Stabilizes TIM-4 and Promotes the Metastasis of NSCLC.Frontiers in oncology · 2022Article
- TIM-4 in macrophages contributes to nasal polyp formation through the TGF-β1-mediated epithelial to mesenchymal transition in nasal epithelial cells.Frontiers in immunology · 2022Article
- The expression and significance of efferocytosis and immune checkpoint related molecules in pancancer samples and the correlation of their expression with anticancer drug sensitivity.Frontiers in pharmacology · 2022Article
- T-Cell Immunoglobulin and Mucin Domain-Containing Protein-4 Is Critical for Kupffer Cell Homeostatic Function in the Activation and Resolution of Liver Ischemia Reperfusion Injury.Hepatology (Baltimore, Md.) · 2021Article
- Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundT-cell immunoglobulin domain and mucin domain 4 (TIM-4) is exclusively expressed in antigen-presenting cells and involved in immune regulation. However, the role of TIM-4 expressed in tumour cells remains completely unknown.
methodsImmunohistochemistry staining was used to examine TIM-4 or Ki-67 expression in tumour tissues. Real-time PCR or RT-PCR was performed to detect TIM-4 mRNA expression. Lung cancer cell growth and proliferation were conducted by CCK-8 assay and EdU staining. Cell cycle progression was analysed by flow cytometry. The PCNA and cell cycle-related proteins were verified by western blot. Co-IP assay was used to identify the interaction of TIM-4 and integrin αvβ3. The efficacy of TIM-4 in vivo was evaluated using xenograft tumour model.
resultsThe expression of TIM-4 in non-small-cell lung cancer (NSCLC) tissues was significantly higher than that of the adjacent tissues. Enhanced TIM-4 expression was negatively correlated with histological differentiation of lung carcinoma and lifespan of patients. Overexpression of TIM-4 promoted lung cancer cell growth and proliferation, and upregulated the expression of PCNA, cyclin A, cyclin B1 and cyclin D1, accompanied by accumulation of lung cancer cells in S phase. Interestingly, Arg-Gly-Asp (RGD) motif mutation abolished the effect of TIM-4 on lung cancer cells, which was further verified by tumour xenografts in mice. Furthermore, we found that TIM-4 interacted with αvβ3 integrin through RGD motif.
conclusionsThis finding suggests that TIM-4 might be a potential biomarker for NSCLC that promotes lung cancer progression by RGD motif.
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