Activated Wnt/β-Catenin signaling contributes to E3 ubiquitin ligase EDD-conferred docetaxel resistance in prostate cancer

Publication date: Available online 28 August 2019Source: Life SciencesAuthor(s): Pan Bian, Zhongling Dou, Zhaohui Jia, Wensheng Li, Dong PanAbstractDocetaxel is commonly used to treat hormone-refractory prostate cancer (HRPC), but its clinical efficacy is limited by drug resistance, with the molecular mechanisms remaining elusive. The E3 ubiquitin ligase EDD modifies substrate proteins through ubiquitination and is involved in the regulation of cell proliferation and tumorigenesis. However, its role in docetaxel resistance of prostate cancer is unknown. Here, we show that EDD is upregulated in docetaxel-resistant HRPC cells, as well as in human HRPC treated with docetaxel chemotherapy. Functionally, EDD knockdown resensitizes HRPC cells to docetaxel in vitro and in vivo, and in reverse, EDD overexpression promotes docetaxel resistance. We further show that the Wnt/β-Catenin signaling is activated in docetaxel-resistant HRPC cells, which can be promoted by EDD. Finally, inhibiting Wnt signaling through β-Catenin knockdown remarkably attenuates EDD-mediated docetaxel resistance, suggesting that the activated Wnt/β-Catenin signaling is a key contributor to EDD-conferred docetaxel resistance in HRPC cells. Altogether, our study uncovers a positive role of EDD in docetaxel resistance in prostate cancer, and further links it with the regulation of Wnt/β-Catenin signaling.
Source: Life Sciences - Category: Biology Source Type: research

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Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
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Source: American Journal of Clinical Oncology - Category: Cancer & Oncology Tags: Original Articles: Genitourinary Source Type: research
Acquired docetaxel (Doc) resistance in hormone-refractory prostate cancer (HRPC) remains an ongoing clinical challenge, resulting in failed chemotherapy and tumor recurrence. However, the mechanism of Doc-resistance development in prostate cancer cells is still unclear. Here, we observed a subpopulation of prostate cancer cells, in both Doc-resistant cell lines and the tumors of patients with HRPC, which show stem cell markers and greater tumorigenic potential. Those stem-like prostate cancer cells show high expression of ABCB1, which encodes multidrug resistance-related protein P-glycoprotein, leading to the Doc-resistanc...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
Chemotherapeutic Docetaxel (Doc) is the standard of care for the hormone resistant prostate cancer (HRPC). However, many HRPC patients do not respond to Doc chemotherapy in a long-term treatment because the cancerous tissue acquires resistance to Doc treatment. The molecular mechanism underlying the development of Doc resistance in HRPC remains unclear.
Source: The Journal of Urology - Category: Urology & Nephrology Authors: Tags: Prostate Cancer: Basic Research & Pathophysiology III Source Type: research
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Source: Oncology - Category: Cancer & Oncology Authors: Tags: Oncology Source Type: research
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Source: Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Technologist Student Papers II Source Type: research
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Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Cancer Biology and Signal Transduction Source Type: research
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Source: Therapeutic Advances in Medical Oncology - Category: Cancer & Oncology Authors: Tags: Reviews Source Type: research
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Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: MTA I: Radiopharmaceutical Therapy Posters Source Type: research
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