Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells

Serrano-Rubi, Mauricio; Jimenez, Lidia; Martínez-Rendón, Jacqueline; Cereijido, Marcelino; Ponce, Arturo

doi:10.3390/ijms22010358

Cited by 2 publications

(2 citation statements)

References 86 publications

(36 reference statements)

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“…Furthermore, there is a growing acknowledgment of pathological processes involving NKA’s engagement as a receptor, where its interaction with GCs can either instigate or alleviate these conditions. Notably, cancer emerges as a significant focus, with numerous studies underscoring the impact of the GC–NKA interaction on various aspects of cancer progression, such as proliferation [ 182 ], adhesion [ 267 ], intercellular communication via gap junctions [ 268 ], epithelial–mesenchymal transition, and apoptosis [ 269 ]. Additionally, other disorders unrelated to cancer but of considerable interest, such as obesity [ 222 ], hypertension [ 270 ], and metabolic disorders [ 271 ], as well as neurological conditions like epilepsy and Alzheimer’s disease [ 187 , 272 ], have been implicated.…”

Section: Discussion and Perspectivementioning

confidence: 99%

Na+/K+-ATPase: More than an Electrogenic Pump

Contreras,

Torres-Carrillo,

Flores-Maldonado

et al. 2024

IJMS

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The sodium pump, or Na+/K+-ATPase (NKA), is an essential enzyme found in the plasma membrane of all animal cells. Its primary role is to transport sodium (Na+) and potassium (K+) ions across the cell membrane, using energy from ATP hydrolysis. This transport creates and maintains an electrochemical gradient, which is crucial for various cellular processes, including cell volume regulation, electrical excitability, and secondary active transport. Although the role of NKA as a pump was discovered and demonstrated several decades ago, it remains the subject of intense research. Current studies aim to delve deeper into several aspects of this molecular entity, such as describing its structure and mode of operation in atomic detail, understanding its molecular and functional diversity, and examining the consequences of its malfunction due to structural alterations. Additionally, researchers are investigating the effects of various substances that amplify or decrease its pumping activity. Beyond its role as a pump, growing evidence indicates that in various cell types, NKA also functions as a receptor for cardiac glycosides like ouabain. This receptor activity triggers the activation of various signaling pathways, producing significant morphological and physiological effects. In this report, we present the results of a comprehensive review of the most outstanding studies of the past five years. We highlight the progress made regarding this new concept of NKA and the various cardiac glycosides that influence it. Furthermore, we emphasize NKA’s role in epithelial physiology, particularly its function as a receptor for cardiac glycosides that trigger intracellular signals regulating cell–cell contacts, proliferation, differentiation, and adhesion. We also analyze the role of NKA β-subunits as cell adhesion molecules in glia and epithelial cells.

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Section: Discussion and Perspectivementioning

confidence: 99%

Na+/K+-ATPase: More than an Electrogenic Pump

Contreras,

Torres-Carrillo,

Flores-Maldonado

et al. 2024

IJMS

Self Cite

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“…We found that they both induce GJIC, following the same signaling pathways as ouabain does, albeit with distinct sensitivity [75]. Moreover, we have shown that ouabain induces increased GJIC in cell lines derived from different types of cancer [76]. More recently we found, interestingly, that GJIC is also modulated by prostaglandin E2, through a process that, in principle, did not appear to be related to ouabain [30].…”

Section: Discussionmentioning

confidence: 99%

Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2

Toro

Jimenez

Rubi

et al. 2021

IJMS

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Ouabain is a cardiac glycoside that has been described as a hormone, with interesting effects on epithelial physiology. We have shown previously that ouabain induces gap junctional intercellular communication (GJIC) in wild, sensitive cells (MDCK-S), but not in cells that have become insensitive (MDCK-I) by modifying their Na+-K+-ATPase. We have also demonstrated that prostaglandin E2 (PGE2) is able to induce increased GJIC by a mechanism other than ouabain, that does not depend on Na+-K+-ATPase. In this work we show, by dye transfer assays, that when MDCK-S and MDCK-I are randomly mixed, to form monolayers, the latter stablish GJIC, because of stimulation by a compound released to the extracellular media, by MDCK-S cells, after treatment with ouabain, as evidenced by the fact that monolayers of only MDCK-I cells, treated with a conditioned medium (CM) that is obtained after incubation of MDCK-S monolayers with ouabain, significantly increase their GJIC. The further finding that either (1) pre-treatment with COX-2 inhibitors or (2) addition to CM of antagonists of EP2 receptor abolish CM’s ability to induce GJIC in MDCK-I monolayers indicate that PGE2 is the GJIC-inducing compound. Therefore, these results indicate that, in addition to direct stimulation, mediated by Na+-K+-ATPase, ouabain enhances GJIC indirectly through the paracrine production of PGE2.

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Ouabain Promotes Gap Junctional Intercellular Communication in Cancer Cells

Cited by 2 publications

References 86 publications

Na+/K+-ATPase: More than an Electrogenic Pump

Na+/K+-ATPase: More than an Electrogenic Pump

Ouabain Enhances Gap Junctional Intercellular Communication by Inducing Paracrine Secretion of Prostaglandin E2

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