دورية أكاديمية
Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high‐grade serous ovarian cancer cells
العنوان: | Plasma membrane SK2 channel activity regulates migration and chemosensitivity of high‐grade serous ovarian cancer cells |
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المؤلفون: | Olivier Romito, Aude Lemettre, Aurélie Chantôme, Ophélie Champion, Noémie Couty, Lobna Ouldamer, Nadine Hempel, Mohamed Trebak, Caroline Goupille, Marie Potier‐Cartereau |
المصدر: | Molecular Oncology, Vol 18, Iss 8, Pp 1853-1865 (2024) |
بيانات النشر: | Wiley, 2024. |
سنة النشر: | 2024 |
المجموعة: | LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
مصطلحات موضوعية: | cell migration, chemosensitivity, high‐grade serous ovarian cancer, LPA, SK2 channel, Taxol®, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
الوصف: | No data are currently available on the functional role of small conductance Ca2+‐activated K+ channels (SKCa) in ovarian cancer. Here, we characterized the role of SK2 (KCa2.2) in ovarian cancer cell migration and chemosensitivity. Using the selective non‐cell‐permeant SK2 inhibitor Lei‐Dab7, we identified functional SK2 channels at the plasma membrane, regulating store‐operated Ca2+ entry (SOCE) in both cell lines tested (COV504 and OVCAR3). Silencing KCNN2 with short interfering RNA (siRNA), or blocking SK2 activity with Lei‐Dab7, decreased cell migration. The more robust effect of KCNN2 knockdown compared to Lei‐Dab7 treatment suggested the involvement of functional intracellular SK2 channels in both cell lines. In cells treated with lysophosphatidic acid (LPA), an ovarian cancer biomarker of progression, SK2 channels are a key player of LPA pro‐migratory activity but their role in SOCE is abolished. Concerning chemotherapy, SK2 inhibition increased chemoresistance to Taxol® and low KCNN2 mRNA expression was associated with the worst prognosis for progression‐free survival in patients with serous ovarian cancer. The dual roles of SK2 mean that SK2 activators could be used as an adjuvant chemotherapy to potentiate treatment efficacy and SK2 inhibitors could be administrated as monotherapy to limit cancer cell dissemination. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1878-0261 1574-7891 |
Relation: | https://doaj.org/toc/1574-7891; https://doaj.org/toc/1878-0261 |
DOI: | 10.1002/1878-0261.13631 |
URL الوصول: | https://doaj.org/article/9b4055aa053c49139808a9db354ee945 |
رقم الأكسشن: | edsdoj.9b4055aa053c49139808a9db354ee945 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 18780261 15747891 |
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DOI: | 10.1002/1878-0261.13631 |