Purinergic Activation of Store-Operated Calcium Entry (SOCE) Regulates Cell Migration in Metastatic Ovarian Cancer Cells

Sep 24, 2026

Store-operated calcium entry (SOCE) is a key mechanism in calcium signaling, with roles in both physiological and pathological processes. In cancer, the relationship between SOCE and aggressiveness, including regulation by purinergic molecules, is not fully clarified. This study compares metastatic (SKOV-3) and non-metastatic (CAOV-3) ovarian cell lines, assessing P2Y2-driven intracellular calcium under normal and zero extracellular calcium conditions. Sustained SOCE is linked to SKOV-3 behavior and inhibits migration when blocked by 2-APB, supporting a role in metastatic aggressiveness.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Keywords

1. Introduction

Transcoelomic dissemination and the tumor microenvironment

Purinergic signaling as a component of the tumor microenvironment

P2 receptor families and P2Y2-mediated pathways

P2Y2 roles in proliferation and migration

pharmaceuticals Article Purinergic Activation of Store-Operated Calcium Entry (SOCE) Regulates Cell Migration in Metastatic Ovarian Cancer Cells Esperanza Mata-Mart½nez 1, Adriana Gonzalez-Gallardo 2, Mauricio D½az-Muñoz 1, * and Francisco G. V¡zquez-Cuevas 1, * Citation: Mata-Martínez, E.; Gonzalez-Gallardo, A.; Díaz-Muñoz, M.; Vázquez-Cuevas, F.G. Purinergic Activation of Store-Operated Calcium Entry (SOCE) Regulates Cell Migration in Metastatic Ovarian Cancer Cells. Pharmaceuticals 2023, 16, 944. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ph16070944 Academic Editor: Massimiliano Tognolini Received: 27 April 2023 Revised: 19 June 2023 Accepted: 27 June 2023 Published: 29 June 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) . 1 Departamento de Neurobiolog½a Celular y Molecular, Universidad Nacional Autânoma de M²xico, Boulevard Juriquilla\#3001, Juriquilla 76230, Quer²taro, Mexico; [espemmtz@gmail.com](espemmtz@gmail.com) 2 Unidad de Proteogenâmica, Instituto de Neurobiolog½a, Universidad Nacional Autânoma de M²xico, Boulevard Juriquilla\#3001, Juriquilla 76230, Quer²taro, Mexico; [gallardog@unam.mx](gallardog@unam.mx) * [Correspondence: mdiaz@comunidad.unam.mx](Correspondence: mdiaz@comunidad.unam.mx) (M.D.-M.); [fvazquez@comunidad.unam.mx](fvazquez@comunidad.unam.mx) (F.G.V.-C.) Abstract: 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 􀀖M and inhibited by ARC118925XX of 1 􀀖M) 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 DF) and sensitive to 2-APB (20.60 􀀆 0.85 DF)), whereas its absence in CAOV-3 cells (26.2 􀀆 6.1 DF) 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. Keywords: purinergic signaling; store-operated calcium entry; P2Y2 receptor; ovarian carcinoma; SKOV-3; cell migration 1. Introduction Ovarian carcinoma (OvCa) is the most lethal gynecological disease [1]; this lethality is caused in part by its high metastatic potential, supported by a particular mechanism named transcoelomic dissemination that involves phenotypic changes in cancer cells orchestrated by a variety of factors within the tumor microenvironment (TME) [2] . Therefore, understanding the TME-dependent mechanisms regulating cell migration in metastatic OvCa cells may contribute to the deﬁnition of oncogenic processes, and eventually to the discovery of new therapeutic targets. The purinergic system has been recognized as an important element of TME; for example, actions of extracellular ATP and its metabolites contribute to tumor progression [3] since cancer cells exhibit adaptations in diverse elements that confer efﬁciency to purinergic signaling. Metabolic ad

FAQs

What is the main focus regarding SOCE in metastatic ovarian cancer cells?

The study characterizes how store-operated calcium entry (SOCE) is regulated by purinergic signaling and how this relates to metastatic cell migration and aggressiveness.

How does P2Y2 receptor activation affect intracellular calcium in the two ovarian cell lines?

P2Y2-driven stimulation produces a sustained calcium influx associated with SOCE in metastatic SKOV-3 cells, while this response is absent in non-metastatic CAOV-3 cells.

What experimental evidence links SOCE to migration in metastatic cells?

In SKOV-3 cells, blocking SOCE with 2-APB significantly inhibits UTP-induced cell migration, supporting SOCE involvement in metastatic behavior.

Sep 24, 2026

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