Rörig Linea, Ruckriegl Sophia, Gallwas Julia, Gründker Carsten
University Medical Center Göttingen, Department of Gynecology and Obstetrics, Göttingen, Germany.
University Medical Center Göttingen, Department of Gynecology and Obstetrics, Göttingen, Germany
Cancer Genomics Proteomics. 2025 Jan-Feb;22(1):13-23. doi: 10.21873/cgp.20482.
BACKGROUND/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.
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.
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.
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.
背景/目的：G蛋白偶联雌激素受体1（GPER1）似乎在宫颈鳞状细胞癌（CSCC）中发挥肿瘤抑制作用。GPER1的抑制导致丝氨酸蛋白酶抑制剂E家族成员1（SERPINE1）/纤溶酶原激活物抑制剂1型（PAI-1）的表达显著增加。问题是，SERPINE1/PAI-1在CSCC的GPER1依赖性致瘤潜能中起什么作用。
用GPER1激动剂G1或拮抗剂G36处理SiHa和C33A CSCC细胞。通过RNA干扰抑制SERPINE1/PAI-1的表达，并通过RT-qPCR确认成功。用蛋白质印迹法定量PAI-1的蛋白表达。使用刃天青测定法分析细胞活力，同时使用划痕愈合实验研究细胞迁移。采用集落形成和肿瘤球形成实验检测克隆形成能力。
G1处理后，SiHa和C33A细胞的活力保持不变。细胞迁移呈剂量依赖性降低。SiHa和C33A细胞形成的集落和球体明显更少、更小。此外，G1处理导致SERPINE1/PAI-1的表达降低，而用G36阻断GPER1导致SERPINE1/PAI-1的表达显著增加。在用RNA干扰抑制SiHa细胞中的SERPINE1/PAI-1后，细胞活力未受影响；然而，形成的集落明显更小，形成的球体数量更少且更小。细胞迁移未受影响。
GPER1的激活降低了CSCC细胞的克隆形成能力和迁移能力，并抑制了SERPINE1/PAI-1的表达。CSCC细胞中SERPINE1/PAI-1的抑制降低了致瘤潜能。GPER1可能是CSCC中抑制SERPINE1/PAI-1的合适靶点。然而，SERPINE1/PAI-1似乎不是GPER1调节细胞迁移的决定性因素。
