CCN2 and breast cancer: Intriguingly, previous studies have reported that >30 different GPCRs including GPER were also detected in the nuclei of cells (Gobeil et al., 2006; Boivin et al., 2008; Pupo et al., 2013, 2017; Joyal et al., 2015), where it was shown to be localized to the nucleus of isolated breast cancer-associated fibroblasts (CAFs) and functions as a transcription factor that up-regulates the expression of genes such as c-FOS or CTGF (connective tissue growth factor; Madeo and Maggiolini, 2010; Pupo et al., 2013).