ArticleCell death and differentiation2018
Orai3 calcium channel and resistance to chemotherapy in breast cancer cells: the p53 connection.
Article in Cell death and differentiation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 98 citations in OpenAlex.
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- Resistance to Combined Anthracycline-Taxane Chemotherapy Is Associated with Altered Metabolism and Inflammation in Breast Carcinomas.International journal of molecular sciences · 2024Article
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- Unraveling the Potential Role of NEDD4-like E3 Ligases in Cancer.International journal of molecular sciences · 2022Review
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- Connecting Calcium-Based Nanomaterials and Cancer: From Diagnosis to Therapy.Nano-micro letters · 2022Article
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Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Orai proteins are highly selective calcium channels playing an important role in calcium entry. Orai3 channels are overexpressed in breast cancer (BC) tissues, and involved in their proliferation, cell cycle progression and survival. Herein, we sought to address the involvement of Orai3 in resistance to chemotherapeutic drugs. Using high-throughput approaches, we investigated major changes induced by Orai3 overexpression, including downstream signaling mechanisms involved in BC chemotherapy resistance. Resistance was dependent on external calcium presence and thus Orai3 functionality. This effect allowed a downregulation of the p53 tumor suppressor protein expression via the pro-survival PI3K/Sgk-1/Sek-1 pathway. We demonstrated that p53 degradation occurred not only via Mdm2, but also via another unexpected E3 ubiquitin ligase, Nedd4-2. We found supporting bioinformatic evidence linking Orai3 overexpression and chemoresistance in large human BC data sets. Altogether, our results shed light on the molecular mechanisms activated in BC cells commonly found to overexpress Orai3, allowing resistance to chemotherapeutic drugs.
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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.