Figure 7.

GPER inhibits membrane invasion via the RhoA/ROCK (Rho-associated protein kinase) system. The first step in the metastatic process is the invasion of neighbouring tissues, which requires the cells to breach the basement membrane. In pancreatic and prostate cancer cells, GPER can reduce their ability to breach the basement membrane by acting as a mechanoregulator. Pharmacological activation of GPER using G1 or Tamoxifen inhibits the activity of RhoA, preventing the subsequent activation of ROCK and the formation of phospho-myosin light chain 2 (pMLC-2). By controlling the activity of pMLC-2, GPER activation can modulate the contractile actomyosin machinery and regulate the mechanical activity of the cell.