Aim
G protein-coupled estrogen receptor 1 (GPER1) appears to play a tumor-suppressive role in cervical squamous cell carcinoma (CSCC)GPER1 suppression leads to significantly increased expression of serpin family E member 1 (SERPINE1)/protein plasminogen activator inhibitor type 1 (PAI-1). The question arises, what role does SERPINE1/PAI-1 play in GPER1-dependent tumorigenic potential of CSCC. Materials and
Conclusion
Activation of GPER1 reduces clonogenicity and migration of CSCC cells and suppresses expression of SERPINE1/PAI-1. Suppression of SERPINE1/PAI-1 in CSCC cells reduces tumorigenic potential. GPER1 may be a suitable target for suppression of SERPINE1/PAI-1 in CSCC. However, SERPINE1/PAI-1 does not appear to be the decisive factor for GPER1-regulated cell migration.
Methods
SiHa and C33A CSCC cells were treated with GPER1 agonist G1 or antagonist G36. SERPINE1/PAI-1 expression was suppressed by RNAi and success was confirmed by RT-qPCR. Protein expression of PAI-1 was quantified by Western blot. Viability was analyzed using resazurin assay, while migration was investigated using gap closure. Colony and tumor sphere formation were used to test clonogenicity.
Results
After G1 treatment, viability of SiHa and C33A cells remained unchanged. Cell migration was dose-dependently reduced. SiHa and C33A cells formed significantly fewer and smaller colonies as well as spheroids. Furthermore, treatment with G1 led to decreased expression of SERPINE1/PAI-1, while blockade of GPER1 with G36 resulted in significantly increased SERPINE1/PAI-1 expression. After suppression of SERPINE1/PAI-1 in SiHa cells using RNAi, cell viability remained unaffected; however, significantly smaller colonies were formed, and fewer and smaller spheroids were developed. Cell migration remained unaffected.