Lin, Tsung-HanTsung-HanLinHsu, Wen-HsienWen-HsienHsuTsai, Pei-HsunPei-HsunTsaiHuang, Ying-TangYing-TangHuangLin, Cheng-WeiCheng-WeiLinChen, Ku-ChungKu-ChungChenTsai, Inn-HoInn-HoTsaiKandaswami, Chithan C.Chithan C.KandaswamiHuang, Chang-JenChang-JenHuangGEEN-DONG CHANGLee, Ming-TingMing-TingLeeCheng, Chia-HsiungChia-HsiungCheng2020-01-222020-01-22201720426496https://scholars.lib.ntu.edu.tw/handle/123456789/452627https://www2.scopus.com/inward/record.uri?eid=2-s2.0-85018739590&doi=10.1039%2fc6fo00551a&partnerID=40&md5=2c9c539b42cf3b40922602907cbcd5eeWe previously reported that the dietary flavonoids, luteolin and quercetin, might inhibit the invasiveness of cervical cancer by reversing epithelial-mesenchymal transition (EMT) signaling. However, the regulatory mechanism exerted by luteolin and quercetin is still unclear. This study analyzed the invasiveness activation by ubiquitin E2S ligase (UBE2S) through EMT signaling and inhibition by luteolin and quercetin. We found that UBE2S expression was significantly higher in highly invasive A431 subgroup III (A431-III) than A431-parental (A431-P) cells. UBE2S small interfering (si)RNA knockdown and overexpression experiments showed that UBE2S increased the migratory and invasive abilities of cancer cells through EMT signaling. Luteolin and quercetin significantly inhibited UBE2S expression. UBE2S showed a negative correlation with von Hippel-Lindau (VHL) and a positive correlation with hypoxia-induced factor (Hif)-1α. Our findings suggest that high UBE2S in malignant cancers contributes to cell motility through EMT signaling and is reversed by luteolin and quercetin. UBE2S might contribute to Hif-1α signaling in cervical cancer. These results show the metastatic inhibition of cervical cancer by luteolin and quercetin through reducing UBE2S expression, and provide a functional role for UBE2S in the motility of cervical cancer. UBE2S could be a potential therapeutic target in cervical cancer. ? 2017 The Royal Society of Chemistry.[SDGs]SDG2[SDGs]SDG3Cell signaling; Complexation; Diseases; Phenols; Signaling; Cervical cancers; Epithelial-mesenchymal transition; Malignant cancers; Negative correlation; Positive correlations; Regulatory mechanism; Therapeutic targets; Von hippel lindau; Flavonoids; luteolin; quercetin; Ube2S protein, human; ubiquitin conjugating enzyme; analysis; dietary supplement; drug effects; epithelial mesenchymal transition; female; genetics; human; metabolism; pathophysiology; signal transduction; tumor cell line; tumor invasion; Uterine Cervical Neoplasms; Cell Line, Tumor; Dietary Supplements; Epithelial-Mesenchymal Transition; Female; Humans; Luteolin; Neoplasm Invasiveness; Quercetin; Signal Transduction; Ubiquitin-Conjugating Enzymes; Uterine Cervical Neoplasmsjournal article10.1039/c6fo00551a282775812-s2.0-85018739590