Mata-Martínez Esperanza, Gonzalez-Gallardo Adriana, Díaz-Muñoz Mauricio, Vázquez-Cuevas Francisco G
Departamento de Neurobiología Celular y Molecular, Universidad Nacional Autónoma de México, Boulevard Juriquilla#3001, Juriquilla 76230, Querétaro, Mexico.
Unidad de Proteogenómica, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Boulevard Juriquilla#3001, Juriquilla 76230, Querétaro, Mexico.
Pharmaceuticals (Basel). 2023 Jun 29;16(7):944. doi: 10.3390/ph16070944.
Store-operated calcium entry (SOCE) is an important process in calcium signaling. Its role in physiological and pathological events is well recognized. However, in cancerous systems, the importance of SOCE in relation to the degree of cancer aggressiveness, as well as its regulation by ligands such as purinergic molecules, are not well documented. This study aimed to characterize a differential effect of the P2Y2 receptor (promoted by UTP of 10 µM and inhibited by ARC118925XX of 1 µM) on intracellular calcium response between metastatic (SKOV-3) and non-metastatic (CAOV-3) ovarian cell lines in conditions of normal (1.5 mM) and zero extracellular calcium concentration. The sustained calcium influx observed exclusively in SKOV-3 cells was associated with the presence of SOCE (promoted by thapsigargin (74.81 ± 0.94 ΔF) and sensitive to 2-APB (20.60 ± 0.85 ΔF)), whereas its absence in CAOV-3 cells (26.2 ± 6.1 ΔF) was correlated with a low expression of ORAI1. The relevance of SOCE in metastatic SKOV-3 cells was further corroborated when 2-APB significantly inhibited (40.4 ± 2.8% of covered area) UTP-induced cell migration (54.6 ± 3.7% of covered area). In conclusion, our data suggest that SOCE activation elicited by the P2Y2 receptor is involved in the aggressiveness of ovarian cancer cells.
store-operated calcium entry (SOCE)是钙信号传导中的一个重要过程。其在生理和病理事件中的作用已得到充分认识。然而，在癌症系统中，SOCE与癌症侵袭程度的关系及其受嘌呤能分子等配体调控的重要性，目前尚无充分记录。本研究旨在表征P2Y2受体（由10 μM的UTP促进，由1 μM的ARC118925XX抑制）在正常（1.5 mM）和零细胞外钙浓度条件下对转移性（SKOV-3）和非转移性（CAOV-3）卵巢细胞系细胞内钙反应的差异影响。仅在SKOV-3细胞中观察到的持续钙内流与SOCE的存在相关（由毒胡萝卜素促进（74.81±0.94 ΔF），对2-APB敏感（20.60±0.85 ΔF）），而CAOV-3细胞中不存在（26.2±6.1 ΔF）则与ORAI1的低表达相关。当2-APB显著抑制（覆盖面积的40.4±2.8%）UTP诱导的细胞迁移（覆盖面积的54.6±3.7%）时，进一步证实了SOCE在转移性SKOV-3细胞中的相关性。总之，我们的数据表明，P2Y2受体引发的SOCE激活与卵巢癌细胞的侵袭性有关。
