ArticlePloS one2014
Down-regulation of Gli transcription factor leads to the inhibition of migration and invasion of ovarian cancer cells via integrin β4-mediated FAK signaling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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50 citing papers in PubMed, 77 citations in OpenAlex.
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- Identification of the biological functions and chemo-therapeutic responses of ITGB superfamily in ovarian cancer.Discover oncology · 2024Article
- Oncofetal reprogramming in tumor development and progression: novel insights into cancer therapy.MedComm · 2023Review
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Modulation of Hedgehog Signaling for the Treatment of Basal Cell Carcinoma and the Development of Preclinical Models.Biomedicines · 2022Review
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- Evaluation of Hedgehog Pathway Inhibitors as a Therapeutic Option for Uterine Leiomyosarcoma Using the Xenograft Model.Reproductive sciences (Thousand Oaks, Calif.) · 2022Article
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- Identification of prognostic and bone metastatic alternative splicing signatures in bladder cancer.Bioengineered · 2021Article
- Basal epidermis collective migration and local Sonic hedgehog signaling promote skeletal branching morphogenesis in zebrafish fins.Developmental biology · 2021Article
- Targeting Hedgehog signalling in CD133-positive hepatocellular carcinoma: improving Lenvatinib therapeutic efficiency.Medical oncology (Northwood, London, England) · 2021Article
- A Pan-Cancer Analysis of the Oncogenic Role of Integrin Beta4 (ITGB4) in Human Tumors.International journal of general medicine · 2021Article
- Intertwined Signaling Pathways Governing Tooth Development: A Give-and-Take Between Canonical Wnt and Shh.Frontiers in cell and developmental biology · 2021Review
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- The Hedgehog signaling pathway promotes chemotherapy resistance via multidrug resistance protein 1 in ovarian cancer.Oncology reports · 2020Article
- Characterization of the prognostic and oncologic values of ITGB superfamily members in pancreatic cancer.Journal of cellular and molecular medicine · 2020Article
- Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update.Nature reviews. Clinical oncology · 2020Review
- Integrated Analysis of Prognostic and Immune Associated Integrin Family in Ovarian Cancer.Frontiers in genetics · 2020Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundRecent evidence suggests that aberrant activation of Hedgehog (Hh) signaling by Gli transcription factors is characteristic of a variety of aggressive human carcinomas including ovarian cancer. Therefore, chemotherapeutic agents that inhibit activation of Gli transcription factors have emerged as promising novel therapeutic drugs for ovarian cancer.
resultsIn this study, we show that activation of Hh signaling promoted cellular migration and invasion, whereas blockade of Hh signaling with GANT61 suppressed cellular migration and invasion in ovarian cancer cells. After treatment with GANT61, cDNA microarray analyses revealed changes in many genes such as Integrin β4 subunit (ITGB4), focal adhesion kinase (FAK), etc. Furthermore, ITGB4 expression was up-regulated by Sonic Hedgehog (Shh) ligand and down-regulated by Hh signaling inhibitor. The Shh-mediated ovarian cell migration and invasion was blocked by neutralizing antibodies to ITGB4. In addition, phosphorylations of FAK were increased by Shh and decreased by Hh signaling inhibitor. Inhibition of Gli1 expression using siRNA mimicked the effects of GANT61 treatment, supporting the specificity of GANT61. Further investigations showed that activation of FAK was required for Shh-mediated cell migration and invasion. Finally, we found that down-regulation of Gli reduced the expression of ITGB4 and the phosphorylated FAK, resulting in the inhibition of tumor growth in vivo.
conclusionsThe Hh signaling pathway induces cell migration and invasion through ITGB4-mediated activation of FAK in ovarian cancer. Our findings suggest that the diminishment of crosstalk between phosphorylated FAK and ITGB4 due to the down-regulation of Gli family transcription factors might play a pivotal role for inhibiting ovarian cancer progression.
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