GPER1 is regulated by insulin in cancer cells and cancer associated fibroblasts

摘要: Elevated insulin levels have been associated with an increased cancer risk as well aggressive and metastatic phenotypes characterized by a poor prognosis. Insulin stimulates the proliferation, migration, invasiveness of cells through diverse transduction pathways, including estrogen signaling. As G protein receptor 1 (GPER1) mediates rapid cell responses to estrogens, we evaluated potential regulate GPER1 expression function in leiomyosarcoma (SKUT-1) breast cancer-associated fibroblasts (CAFs), which were used model system. We found that transactivates promoter sequence increases mRNA activation PRKCD/MAPK1/c-Fos/AP1 pathway, ascertained means specific pharmacological inhibitors gene-silencing experiments. Moreover, migration triggered occurred its main target gene CTGF, whereas insulin-induced boosted cell-cycle progression glucose uptake stimulated estrogens. Notably, positive correlation between serum was obtained from patients. Altogether, our data indicate may be included among complex network signaling drives toward progression.