ArticleCell death & disease2015
ARHI (DIRAS3)-mediated autophagy-associated cell death enhances chemosensitivity to cisplatin in ovarian cancer cell lines and xenografts.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 62 citations in OpenAlex.
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- Differential effects of the LncRNA RNF157-AS1 on epithelial ovarian cancer cells through suppression of DIRAS3- and ULK1-mediated autophagy.Cell death & disease · 2023Article
- Autophagy Inhibition Contributes to Apoptosis of PLK4 Downregulation-induced Dormant Cells in Colorectal Cancer.International journal of biological sciences · 2023Article
- Is Autophagy Always a Barrier to Cisplatin Therapy?Biomolecules · 2022Review
- GTP-binding protein Di-RAS3 diminishes the migration and invasion of non-small cell lung cancer by inhibiting the RAS/extracellular-regulated kinase pathway.Bioengineered · 2022Article
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- DIRAS3, GPR171 and RAC2 were identified as the key molecular patterns associated with brain metastasis of breast cancer.Frontiers in oncology · 2022Article
- Autophagy and Hepatic Tumor Microenvironment Associated Dormancy.Journal of gastrointestinal cancer · 2021Review
- The Emerging Roles of Autophagy in Human Diseases.Biomedicines · 2021Review
- The mTOR Pathway in Pluripotent Stem Cells: Lessons for Understanding Cancer Cell Dormancy.Membranes · 2021Review
- Frequent Epigenetic Inactivation of DIRAS-1 and DIRAS-2 Contributes to Chemo-Resistance in Gliomas.Cancers · 2021Article
- trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway.Scientific reports · 2021Article
- Autophagy and Cancer Dormancy.Frontiers in oncology · 2021Review
- Re-expression of DIRAS3 and p53 induces apoptosis and impaired autophagy in head and neck squamous cell carcinoma.Military Medical Research · 2020Article
- Article
- A risk signature with four autophagy-related genes for predicting survival of glioblastoma multiforme.Journal of cellular and molecular medicine · 2020Article
- Alisol A Suppresses Proliferation, Migration, and Invasion in Human Breast Cancer MDA-MB-231 Cells.Molecules (Basel, Switzerland) · 2019Article
- A Comparative Study of ARHI Imprinted Gene Detection and Fine-Needle Aspiration Cytology in the Differential Diagnosis of Benign and Malignant Thyroid Nodules.Genetic testing and molecular biomarkers · 2019Article
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13 authors at 1 institution in 1 country.
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Abstract
Autophagy can sustain or kill tumor cells depending upon the context. The mechanism of autophagy-associated cell death has not been well elucidated and autophagy has enhanced or inhibited sensitivity of cancer cells to cytotoxic chemotherapy in different models. ARHI (DIRAS3), an imprinted tumor suppressor gene, is downregulated in 60% of ovarian cancers. In cell culture, re-expression of ARHI induces autophagy and ovarian cancer cell death within 72 h. In xenografts, re-expression of ARHI arrests cell growth and induces autophagy, but does not kill engrafted cancer cells. When ARHI levels are reduced after 6 weeks, dormancy is broken and xenografts grow promptly. In this study, ARHI-induced ovarian cancer cell death in culture has been found to depend upon autophagy and has been linked to G1 cell-cycle arrest, enhanced reactive oxygen species (ROS) activity, RIP1/RIP3 activation and necrosis. Re-expression of ARHI enhanced the cytotoxic effect of cisplatin in cell culture, increasing caspase-3 activation and PARP cleavage by inhibiting ERK and HER2 activity and downregulating XIAP and Bcl-2. In xenografts, treatment with cisplatin significantly slowed the outgrowth of dormant autophagic cells after reduction of ARHI, but the addition of chloroquine did not further inhibit xenograft outgrowth. Taken together, we have found that autophagy-associated cancer cell death and autophagy-enhanced sensitivity to cisplatin depend upon different mechanisms and that dormant, autophagic cancer cells are still vulnerable to cisplatin-based chemotherapy.
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