ArticleOncotarget2015
Bortezomib-mediated down-regulation of telomerase and disruption of telomere homeostasis contributes to apoptosis of malignant cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- The Relationship Between Immunogenic Cell Death and Cellular Senescence in Cancer Immunotherapy.Life (Basel, Switzerland) · 2026Review
- TIMELESS as a prognostic biomarker and therapeutic target in gastric cancer.Journal, genetic engineering & biotechnology · 2025Article
- Targeting Telomere Dynamics as an Effective Approach for the Development of Cancer Therapeutics.International journal of nanomedicine · 2024Review
- Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).Cancer cell international · 2023Review
- Genomic, epigenomic, and transcriptomic signatures for telomerase complex components: a pan-cancer analysis.Molecular oncology · 2023Article
- The anti-tumor effect of proteasome inhibitor MG132 for human adenoid cystic carcinoma: correlate with the emerging role of Nrf2/Keap1 signaling pathway.Head & face medicine · 2022Article
- Thyroid Carcinoma: Phenotypic Features, Underlying Biology and Potential Relevance for Targeting Therapy.International journal of molecular sciences · 2021Review
- Telomerase reverse transcriptase promoter mutations in thyroid carcinomas: implications in precision oncology-a narrative review.Annals of translational medicine · 2020Review
- The telomerase gene polymorphisms, but not telomere length, increase susceptibility to primary glomerulonephritis/end stage renal diseases in females.Journal of translational medicine · 2020Article
- Telomerase Reverse Transcriptase (TERT) in Action: Cross-Talking with Epigenetics.International journal of molecular sciences · 2019Review
- MYC-dependent downregulation of telomerase by FLT3 inhibitors is required for their therapeutic efficacy on acute myeloid leukemia.Annals of hematology · 2018Article
- Telomerase and drug resistance in cancer.Cellular and molecular life sciences : CMLS · 2017Review
- Telomere length is positively associated with the expression of IL‑6 and MIP‑1α in bone marrow mesenchymal stem cells of multiple myeloma.Molecular medicine reports · 2017Article
- Association Between the Telomerase rs2736098_TT Genotype and a Lower Risk of Chronic Hepatitis B and Cirrhosis in Chinese Males.Clinical and translational gastroenterology · 2017Article
- Bortezomib-resistance is associated with increased levels of proteasome subunits and apoptosis-avoidance.Oncotarget · 2016Article
- TERT rs2736100 genotypes are associated with differential risk of myeloproliferative neoplasms in Swedish and Chinese male patient populations.Annals of hematology · 2016Article
- Therapeutic Targeting of Telomerase.Genes · 2016Review
- Review
- The association between the TERT rs2736100 AC genotype and reduced risk of upper tract urothelial carcinomas in a Han Chinese population.Oncotarget · 2016Article
- Induction of MAPK- and ROS-dependent autophagy and apoptosis in gastric carcinoma by combination of romidepsin and bortezomib.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bortezomib inhibits the ubiquitin/proteasome pathway to achieve its anti-cancer effect and its well characterized activity is the NF-κB inhibition through which the anti-apoptotic bcl-2 expression is down-regulated and apoptosis is subsequently induced. However, the downstream molecular targets of bortezomib are still incompletely defined. Because telomere stabilization via activation of telomerase, induction of telomerase reverse transcriptase (hTERT) and appropriate expression of shelterin proteins is essential to cancer development and progression, we investigated the effect of bortezomib on telomere homeostasis/function in malignant cells. The bortezomib treatment of leukemic (HEL) and gastric cancer cells (BGC-823) led to significant inhibition of hTERT and telomerase expression, widespread dysregulation of shelterin protein expression, and telomere shortening, thereby triggering telomere dysfunction and DNA damage. hTERT over-expression attenuated bortezomib-induced telomere shortening, abnormal shelterin expression and telomere dysfunction. Importantly, bortezomib-mediated apoptosis of malignant cells was partially prevented by hTERT over-expression. Mechanistically, hTERT first robustly enhances bcl2 expression and maintains significantly high residual levels of bcl2 even in bortezomib-treated HEL cells. Second, hTERT protects against bortezomib-induced DNA damage. Our findings collectively reveal a profound impact of bortezomib on telomere homeostasis/function. Down-regulation of hTERT expression and telomere dysfunction induced by bortezomib both contribute to its cancer cell killing actions. It is evident from the present study that hTERT can confer resistance of malignant cells to bortezomib-based target cancer therapy, which may have important clinical implications.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.