Resumen
The tumor microenvironment has a strong impact on the behavior of tumor cells. One major cell type residing in the tumor microenvironment is the carcinoma-associated fibroblast (CAF). We were interested in the effect of CAFs on Sox2 (sex determining region Y (SRY)-box 2), which not only is an essential embryonal stem cell transcription factor, but also plays a role in cancer stem cell activity. We found that long-term exposure of ERa-positive breast cancer cells to the cocktail of CAF-secreted factors strongly increased Sox2 expression involving tumor-related proteins and signaling pathways. However, Sox2 was not only present in those tumor cells that express stem cell markers, but was equally abundant in other tumor cells. By being widely expressed, Sox2 may have functions in non-stem cells. In fact, Sox2 was found to regulate ERa expression, to act anti-apoptotically, to promote cellular growth and to protect cells against the anti-estrogen fulvestrant.