ArticleCancer research2010
Downregulation of HtrA1 promotes resistance to anoikis and peritoneal dissemination of ovarian cancer cells.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Exploring the Role of HtrA Family Genes in Cancer: A Systematic Review.Molecular diagnosis & therapy · 2024Pooled it
- Context-dependent roles of HtrA2/Omi in ovarian cancer: mitochondrial apoptotic function linking platinum sensitivity and acquired chemoresistance-a narrative review.Translational cancer research · 2026Review
- Mass Spectrometric Analysis of Clomiphene Citrate-induced Changes in the Secretome Profile of PAX8-positive Human Fallopian Tube Secretory Epithelial Cells and Identification of Biomarkers Relevant to Reproduction and Pregnancy.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Metabolic reprogramming and signaling adaptations in anoikis resistance: mechanisms and therapeutic targets.Molecular and cellular biochemistry · 2025Review
- Systematic analysis of anoikis-related genes identifies SRPX2-FAK/AKT-IL-6 axis in the progression and peritoneal metastasis of gastric cancer.Frontiers in genetics · 2025Article
- Progress in the Study of the Role and Mechanism of HTRA1 in Diseases Related to Vascular Abnormalities.International journal of general medicine · 2024Review
- EZH2 Contributes to Anoikis Resistance and Promotes Epithelial Ovarian Cancer Peritoneal Metastasis by Regulating m6A.Current medical science · 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
- High temperature requirement A1 in cancer: biomarker and therapeutic target.Cancer cell international · 2021Review
- Ginsenosides Rk1 and Rg5 inhibit transforming growth factor-β1-induced epithelial-mesenchymal transition and suppress migration, invasion, anoikis resistance, and development of stem-like features in lung cancer.Journal of ginseng research · 2021Article
- Expression of HTRA Genes and Its Association with Microsatellite Instability and Survival of Patients with Colorectal Cancer.International journal of molecular sciences · 2020Article
- Molecular structure and the role of high-temperature requirement protein 1 in skeletal disorders and cancers.Cell proliferation · 2020Review
- Identification and Analysis of Glioblastoma Biomarkers Based on Single Cell Sequencing.Frontiers in bioengineering and biotechnology · 2020Article
- HtrA1 upregulates the expression of ADAMTS-5 in HNPCs via the ERK/NF-κB/JNK signaling pathway.American journal of translational research · 2019Article
- HtrA1 expression and the prognosis of high-grade serous ovarian carcinoma: a cohort study using digital analysis.Diagnostic pathology · 2018Article
- Inactivation of the serine protease HTRA1 inhibits tumor growth by deregulating angiogenesis.Oncogene · 2018Article
- Protective effects of an HTRA1 insertion-deletion variant against age-related macular degeneration in the Chinese populations.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- The differential role of HTRA1 in HPV-positive and HPV-negative cervical cell line proliferation.BMC cancer · 2016Article
- Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression.Oncotarget · 2016Article
- Serine protease inhibitor Kazal type 1 (SPINK1) drives proliferation and anoikis resistance in a subset of ovarian cancers.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
We previously identified serine protease HtrA1 as a downregulated gene in epithelial ovarian cancer (EOC), but the functional consequence of loss of HtrA1 in EOC remains largely unclear. Here, we report that loss of HtrA1 attenuates anoikis--a critical physiologic barrier for tumor metastasis. In response to loss of anchorage, HtrA1 expression was upregulated in SKOV3 cells, resulting in autocatalytic activation of HtrA1. Stable knockdown of HtrA1 in SKOV3 and TOV21G cells resulted in resistance to anoikis due to enhanced activation of epidermal growth factor receptor (EGFR)/AKT pathway. In suspended SKOV3 cells, enhanced expression of HtrA1 inhibited EGFR/AKT pathway, leading to increased cell death, whereas protease-inactive mutant HtrA1 failed to result in either the inhibition of EGFR/AKT pathway or increased cell death, suggesting the requirement of HtrA1 protease activity in regulating anoikis. Immunoprecipitation and immunofluorescence assays revealed that HtrA1 interacted with EGFR not only on the cell membrane but also in the nucleus. Most importantly, downregulation of HtrA1 significantly enhanced the peritoneal dissemination of SKOV3ip1 cells in nonobese diabetic/severe combined immunodeficient mice, with increased phospho-EGFR level in corresponding tumor nodules compared with that in xenografts originated from the control cells. Taken together, these data reveal for the first time a novel function of HtrA1 in promoting anoikis by attenuating activation of EGFR/AKT pathway that may contribute to its metastasis suppression capacity, thus providing a possible explanation for the aggressive nature of human ovarian tumors with downregulated HtrA1.
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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.