ArticleBMC cancer2014
Interaction of translationally controlled tumor protein with Apaf-1 is involved in the development of chemoresistance in HeLa cells.
Article in BMC cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Pharmacological Modulators of TCTP: Opportunities and Challenges for Drug Repurposing.International journal of molecular sciences · 2026Review
- Nutritional approaches in combating therapeutic resistance and enhancing treatment efficacy in cancer: the impact of ketogenic diets.Nutrition & metabolism · 2025Review
- Biological role and expression of translationally controlled tumor protein (TCTP) in tumorigenesis and development and its potential for targeted tumor therapy.Cancer cell international · 2024Review
- Review
- [Galectin-1 knockdown inhibits proliferation, migration, invasion and promotes apoptosis of lung adenocarcinoma cellsNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Targeting TCTP sensitizes tumor to T cell-mediated therapy by reversing immune-refractory phenotypes.Nature communications · 2022Article
- Protective Effects ofMarine drugs · 2021Article
- Topoisomerase II is regulated by translationally controlled tumor protein for cell survival during organ growth in Drosophila.Cell death & disease · 2021Article
- Upregulation of Translationally Controlled Tumor Protein Is Associated With Cervical Cancer Progression.Frontiers in molecular biosciences · 2021Article
- Review
- Radiosensitivity of Cancer Cells Is Regulated by Translationally Controlled Tumor Protein.Cancers · 2019Article
- TPT1 (tumor protein, translationally-controlled 1) negatively regulates autophagy through the BECN1 interactome and an MTORC1-mediated pathway.Autophagy · 2017Article
- Translationally controlled tumour protein TCTP is induced early in human colorectal tumours and contributes to the resistance of HCT116 colon cancer cells to 5-FU and oxaliplatin.Cell communication and signaling : CCS · 2017Article
- Article
- RNA interference‑mediated knockdown of translationally controlled tumor protein induces apoptosis, and inhibits growth and invasion in glioma cells.Molecular medicine reports · 2015Article
- Insulin induces phosphorylation of serine residues of translationally controlled tumor protein in 293T cells.International journal of molecular sciences · 2015Article
- Phospho-TCTP as a therapeutic target of Dihydroartemisinin for aggressive breast cancer cells.Oncotarget · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTranslationally controlled tumor protein (TCTP), alternatively called fortilin, is believed to be involved in the development of the chemoresistance of tumor cells against anticancer drugs such as etoposide, taxol, and oxaliplatin, the underlying mechanisms of which still remain elusive.
methodsCell death analysis of TCTP-overexpressing HeLa cells was performed following etoposide treatment to assess the mitochondria-dependent apoptosis. Apoptotic pathway was analyzed through measuring the cleavage of epidermal growth factor receptor (EGFR) and phospholipase C-γ (PLC-γ), caspase activation, mitochondrial membrane perturbation, and cytochrome c release by flow cytometry and western blotting. To clarify the role of TCTP in the inhibition of apoptosome, in vitro apoptosome reconstitution and immunoprecipitation was used. Pull-down assay and silver staining using the variants of Apaf-1 protein was applied to identify the domain that is responsible for its interaction with TCTP.
resultsIn the present study, we confirmed that adenoviral overexpression of TCTP protects HeLa cells from cell death induced by cytotoxic drugs such as taxol and etoposide. TCTP antagonized the mitochondria-dependent apoptotic pathway following etoposide treatment, including mitochondrial membrane damage and resultant cytochrome c release, activation of caspase-9, and -3, and eventually, the cleavage of EGFR and PLC-γ. More importantly, TCTP interacts with the caspase recruitment domain (CARD) of Apaf-1 and is incorporated into the heptameric Apaf-1 complex, and that C-terminal cleaved TCTP specifically associates with Apaf-1 of apoptosome in apoptosome-forming condition thereby inhibiting the amplification of caspase cascade.
conclusionsTCTP protects the cancer cells from etoposide-induced cell death by inhibiting the mitochondria-mediated apoptotic pathway. Interaction of TCTP with Apaf-1 in apoptosome is involved in the molecular mechanism of TCTP-induced chemoresistance. These findings suggest that TCTP may serve as a therapeutic target for chemoresistance in cancer treatment.
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