ArticleThe Journal of biological chemistry2010
High temperature requirement A3 (HtrA3) promotes etoposide- and cisplatin-induced cytotoxicity in lung cancer cell lines.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review.Molecular diagnosis & therapy · 2024Pooled it
- Host andGut microbes · 2026Article
- Htra4 promotes vascular endothelial cell injury and is associated with the early-onset of preeclampsia.Scientific reports · 2025Article
- Genome mining of albocandins A-E fromRSC advances · 2025Article
- HtrA3 paves the way for MSC migration and promotes osteogenesis.Bioactive materials · 2024Article
- Identification of MicroRNAs RegulatingCurrent issues in molecular biology · 2023Article
- Overview of Human HtrA Family Proteases and Their Distinctive Physiological Roles and Unique Involvement in Diseases, Especially Cancer and Pregnancy Complications.International journal of molecular sciences · 2021Review
- Quinacrine Induces Nucleolar Stress in Treatment-Refractory Ovarian Cancer Cell Lines.Cancers · 2021Article
- Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.International journal of molecular sciences · 2020Article
- A distinct concerted mechanism of structural dynamism defines activity of human serine protease HtrA3.The Biochemical journal · 2020Article
- CSB promoter downregulation via histone H3 hypoacetylation is an early determinant of replicative senescence.Nature communications · 2019Article
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- Maternal HtrA3 optimizes placental development to influence offspring birth weight and subsequent white fat gain in adulthood.Scientific reports · 2017Article
- Paeoniflorin suppresses pancreatic cancer cell growth by upregulating HTRA3 expression.Drug design, development and therapy · 2017Article
- High temperature requirement A3 (HTRA3) expression predicts postoperative recurrence and survival in patients with non-small-cell lung cancer.Oncotarget · 2016Article
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- Article
- HtrA3 is negatively correlated with lymph node metastasis in invasive ductal breast cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2013Article
- HtrA3 Is Downregulated in Cancer Cell Lines and Significantly Reduced in Primary Serous and Granulosa Cell Ovarian Tumors.Journal of Cancer · 2013Article
- Human high temperature requirement serine protease A1 (HTRA1) degrades tau protein aggregates.The Journal of biological chemistry · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung cancer is the leading cause of cancer-related deaths worldwide. Here we show for the first time that HtrA3 is a mitochondrial stress-response factor that promotes cytotoxicity to etoposide and cisplatin in lung cancer cell lines. Exogenous expression of wild type HtrA3 domain variants significantly attenuated cell survival with etoposide and cisplatin treatment in lung cancer cell lines H157 and A549 compared with expression of protease inactive mutants (S305A) or vector control. Conversely, HtrA3 suppression promoted cell survival with etoposide and cisplatin treatment in lung cancer cell lines Hop62 and HCC827. Survival was attenuated by re-expression of wild type HtrA3 variants during treatment but not by protease inactive mutants or vector control. HtrA3 also co-fractionated and co-localized with mitochondrial markers with both endogenous and exogenous expression in normal lung and lung cancer cell lines but was translocated from mitochondria following etoposide treatment. Moreover, HtrA3 translocation from mitochondria correlated with an increase in cell death that was attenuated by either HtrA3 suppression or Bcl-2 overexpression. Taken together, these results suggest that HtrA3 may be a previously uncharacterized mitochondrial cell death effector whose serine protease function may be crucial to modulating etoposide- and cisplatin-induced cytotoxicity in lung cancer cell lines.
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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.