Project description:Estrogen is proven to promote the malignant behaviors of many cancers via its receptors. Estrogen receptor alfa 36(ER-α36) is a newly identified isoform of estrogen receptor alfa (ERα), which is different from the 66 kDa estrogen receptor alpha (ER-α66).However, the role of ER-α36 in regulating the effects of estrogen and its potential impact on human cervical cancer is poorly understood. In this study, we found that ER-α36 was over-expressed in cervical cancer tissues and elevated ER-α36 expression was associated with poor prognosis in cervical cancer patients. High expression of ER-α36 promotes the proliferation, invasion and metastasis of cervical cancer cells mediated by estrogen, while silencing ER-α36 had the opposite effects. Further research showed that high mobility group A2 (HMGA2) identified as a down-target of ER-α36 in cervical cancer cells. The oncogenic effect of ER-α36 was attenuated after HMGA2 knockdown. In conclusion, high expression of ER-α36 was correlated with a poor prognosis and metastasis in cervical cancer by regulating HMGA2.ER-α36 might serve as a prognostic biomarker and a target for cervical cancer treatment.
Project description:Cancer Associated Fibroblasts (CAFs) are crucial in the genesis and progression of tumors. Cervical CAFs (C-CAFs) are less well characterized. Estrogen (E2) is considered a cofactor in cervical carcinogenesis. We studied the molecular signature of exvivo cultured C-CAFs from 4 early International Federation of Gynaecology and Obstetrics (FIGO, IB2) and 2 late (IIIA) stage disease using gene expression microarray. We found C-CAFs to be both pro-tumorigenic and moderately inflammatory; late stage C-CAFs were more actively metabolizing, and cycling, but expressed fewer genes related to immune function. We investigated the expression of ERα in exvivo cultured C-CAFs and studied the role of E2 in their biology by gene expression microarray in the presence of two ERα antagonists: ICI 182,780 and Methyl Piperidino Pyrazole (MPP). Both modulated C-CAF function by down regulating genes associated with cell cycle and metabolism, affecting angiogenesis and cancer progression, though their transcriptomes differed. MPP also down regulated genes involved in Epithelial to Mesenchymal Transition. Thus, canonical ERα signaling is vital for C-CAF functioning. Interfering with paracrine signaling through fibroblast ERα may be worth exploiting as a targeted therapy in cervical cancer. Gene expression microarray profiling of 4 early-stage E2 (estrogen) treated, 2 late-stage E2 treated, 2 early-stage ICI (ER-alpha antagonist) treated, 2 late-stage ICI treated and 2 early-stage MPP (ER-alpha antagonist) treated cervical cancer CAFs. E2 treated C-CAFs served as control.
Project description:Estrogen Receptor α (ERα)-mTOR signaling crosstalk rewires cancer cell metabolism providing a mechanism underlying obesity-associated postmenopausal breast cancer [ChIP-seq]
Project description:Estrogen Receptor α (ERα)-mTOR signaling crosstalk rewires cancer cell metabolism providing a mechanism underlying obesity-associated postmenopausal breast cancer [RNA-seq]