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The proliferation, migration, invasion, and cell cycle of human ovarian cancer cell lines SK-OV-3, SW626, and Anglene were evaluated using MTT assays, scratch tests, Transwell assays, and flow cytometry. The effects of IRE1&amp;alpha; inhibition on EOC cell proliferation, migration, and apoptosis were investigated using pharmacological inhibitors and shRNA knockdown. IRE1&amp;alpha; was highly expressed in EOC patients and was negatively correlated with patient survival rates. Additionally, IRE1&amp;alpha; scores in EOC patients were positively correlated with serum levels of TNF-&amp;alpha; and VEGF-a. Compared to normal controls, significantly higher expressions of IRE1&amp;alpha; and XBP1 were observed in ovarian cancer tissues and cells. Knockdown of IRE1&amp;alpha; in ovarian cancer cells led to a significant reduction in the expression of IRE1&amp;alpha; and XBP1s, as well as inhibited cell proliferation and survival. The IRE1&amp;alpha; inhibitors STF-083100 and 4&amp;mu;8C suppressed the proliferation, invasion, and migration of SK-OV-3 cells and reduced the expression levels of related factors. 4&amp;mu;8C inhibited the degradation of YAP within SK-OV-3 cells while downregulating the expression of Cyclin D1 protein. Compared to the group treated with 4&amp;mu;8C alone, the combined intervention of 4&amp;mu;8C and a YAP inhibitor showed a more pronounced inhibitory effect on the proliferation of SK-OV-3 cells.This study first reveals that the IRE1&amp;alpha;\/YAP signal drives the malignant progression of EOC through the regulation of cell proliferation, migration, and invasion. The dual-targeted synergistic inhibition of IRE1&amp;alpha;\/YAP1 offers an innovative therapeutic paradigm for the treatment of EOC.\n<\/p>","DOI":"10.1615\/critrevimmunol.2025057246","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T17:00:56Z","timestamp":1741885256000},"page":"19-32","source":"Crossref","is-referenced-by-count":0,"title":["Dual Inhibition of IRE1&amp;alpha; and YAP Signaling as a Potential Therapy for Epithelial Ovarian Carcinoma"],"prefix":"10.1615","volume":"45","author":[{"given":"Fei","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chunhua","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Buzhen","family":"Tan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linsheng","family":"He","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuan","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"613","reference":[{"key":"2","doi-asserted-by":"crossref","unstructured":"Li X, Ng ASN, Mak VCY, Chan KKL, Cheung ANY, Cheung LWT. 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