Ets-1 expression promotes epithelial cell transformation by inducing migration, invasion and anchorage-independent growth

Abstract

Ets-1 is the prototype of the family of ETS transcription factors. In human tumors, Ets-1 is expressed in endothelial cells and fibroblasts of the tumor stroma and is proposed to play a role in tumor vascularization and invasion by upregulating expression of matrix-degrading proteases. In human carcinomas, Ets-1 is also expressed by neoplastic cells, but little is known about the functional implications of this observation. We have addressed the role of Ets-1 in epithelial HeLa tumor cells by selecting stably Ets-1 over and underexpressing HeLa cells. Ets-1 expression increases the transformed phenotype of HeLa cells, by promoting cell migration, invasion and anchorage-independent growth, while Ets-1 downregulation reduces cell attachment. In correlation with these results, Ets-1 upregulation increases integrinb2 expression but not that of other integrins. These results suggest that, in addition to its role in the tumor stroma, Ets-1 may also promote tumor development and progression by increasing neoplastic transformation.

The role of histamine in human mammary carcinogenesis: H3 and H4 receptors as potential therapeutic targets for breast cancer treatment.

“…44 Coincidently, current studies indicate that histamine is capable of modulating the expression of Ets-1 in MDA-MB-231 cells (data not shown), known as a transcription factor that regulates cell motility. 45 Further studies are needed to elucidate the H3R-associated signal transduction pathways and the H3R isoforms that are expressed in breast tissue. Several H3R isoforms varying in the length of their third intracellular loops have been identified, [23][24][25][26]46 and due to the fact that this molecular domain is thought to be responsible for coupling to G proteins, it is likely that the different H3R isoforms have differences in their signaling pathways.…”

The transforming growth factor beta-1 in the oncogenesis of human lung adenocarcinoma

“…ETS1 сверхэкспрессируется при инвазивном РМЖ и корре-лирует с его плохим прогнозом [38]. Высокая экспрес-сия ETS1 способствует миграции раковых клеток, инвазии и анкернезависимому росту, в то же время низкая экспрессия ETS1 снижала адгезию клеток HeLa [39]. TGF-β1 увеличивал экспрессию ETS1 в клетках А549 в 69,41 раза (см.…”

Identification of immunity-related genes in prostate cancer and potential role of the ETS family of transcription factors in their regulation

“…Binding preferences for distinct sequences flanking the GGAA/T motif facilitate specificity of the individual ETS-factor binding and may explain the unique biological functions of the different ETS factors (22,23). The ETS family is involved in various biological processes, such as development, differentiation, proliferation, apoptosis, migration, tissue remodelling, invasion and angiogenesis in a variety of cell types such as B cells, endothelial cells, fibroblasts as well as neoplastic cells (24)(25)(26)(27)(28).…”