The Two-Way Relationship Between Calcium and Metabolism in Cancer

Calcium ion (Ca2+) signaling is critical to many physiological processes, and its kinetics and subcellular localization are tightly regulated in all cell types. All Ca2+ flux perturbations impact cell function and may contribute to various diseases, including cancer. Several modulators of Ca2+ signa...

Full description

Bibliographic Details
Main Authors: Camille Dejos, Dimitra Gkika, Anna Rita Cantelmo
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-11-01
Series:Frontiers in Cell and Developmental Biology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fcell.2020.573747/full
_version_ 1818244440288919552
author Camille Dejos
Dimitra Gkika
Dimitra Gkika
Anna Rita Cantelmo
author_facet Camille Dejos
Dimitra Gkika
Dimitra Gkika
Anna Rita Cantelmo
author_sort Camille Dejos
collection DOAJ
description Calcium ion (Ca2+) signaling is critical to many physiological processes, and its kinetics and subcellular localization are tightly regulated in all cell types. All Ca2+ flux perturbations impact cell function and may contribute to various diseases, including cancer. Several modulators of Ca2+ signaling are attractive pharmacological targets due to their accessibility at the plasma membrane. Despite this, the number of specific inhibitors is still limited, and to date there are no anticancer drugs in the clinic that target Ca2+ signaling. Ca2+ dynamics are impacted, in part, by modifications of cellular metabolic pathways. Conversely, it is well established that Ca2+ regulates cellular bioenergetics by allosterically activating key metabolic enzymes and metabolite shuttles or indirectly by modulating signaling cascades. A coordinated interplay between Ca2+ and metabolism is essential in maintaining cellular homeostasis. In this review, we provide a snapshot of the reciprocal interaction between Ca2+ and metabolism and discuss the potential consequences of this interplay in cancer cells. We highlight the contribution of Ca2+ to the metabolic reprogramming observed in cancer. We also describe how the metabolic adaptation of cancer cells influences this crosstalk to regulate protumorigenic signaling pathways. We suggest that the dual targeting of these processes might provide unprecedented opportunities for anticancer strategies. Interestingly, promising evidence for the synergistic effects of antimetabolites and Ca2+-modulating agents is emerging.
first_indexed 2024-12-12T14:17:03Z
format Article
id doaj.art-b84be02264bf42afa848a32d07726a79
institution Directory Open Access Journal
issn 2296-634X
language English
last_indexed 2024-12-12T14:17:03Z
publishDate 2020-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Cell and Developmental Biology
spelling doaj.art-b84be02264bf42afa848a32d07726a792022-12-22T00:21:54ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-11-01810.3389/fcell.2020.573747573747The Two-Way Relationship Between Calcium and Metabolism in CancerCamille Dejos0Dimitra Gkika1Dimitra Gkika2Anna Rita Cantelmo3Univ. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, Lille, FranceUniv. Lille, CNRS, INSERM, CHU Lille, Centre Oscar Lambret, UMR 9020-UMR 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, Lille, FranceInstitut Universitaire de France (IUF), Paris, FranceUniv. Lille, Inserm, U1003 - PHYCEL - Physiologie Cellulaire, Lille, FranceCalcium ion (Ca2+) signaling is critical to many physiological processes, and its kinetics and subcellular localization are tightly regulated in all cell types. All Ca2+ flux perturbations impact cell function and may contribute to various diseases, including cancer. Several modulators of Ca2+ signaling are attractive pharmacological targets due to their accessibility at the plasma membrane. Despite this, the number of specific inhibitors is still limited, and to date there are no anticancer drugs in the clinic that target Ca2+ signaling. Ca2+ dynamics are impacted, in part, by modifications of cellular metabolic pathways. Conversely, it is well established that Ca2+ regulates cellular bioenergetics by allosterically activating key metabolic enzymes and metabolite shuttles or indirectly by modulating signaling cascades. A coordinated interplay between Ca2+ and metabolism is essential in maintaining cellular homeostasis. In this review, we provide a snapshot of the reciprocal interaction between Ca2+ and metabolism and discuss the potential consequences of this interplay in cancer cells. We highlight the contribution of Ca2+ to the metabolic reprogramming observed in cancer. We also describe how the metabolic adaptation of cancer cells influences this crosstalk to regulate protumorigenic signaling pathways. We suggest that the dual targeting of these processes might provide unprecedented opportunities for anticancer strategies. Interestingly, promising evidence for the synergistic effects of antimetabolites and Ca2+-modulating agents is emerging.https://www.frontiersin.org/articles/10.3389/fcell.2020.573747/fullcalciumsignalingmetabolisminterplaycancer
spellingShingle Camille Dejos
Dimitra Gkika
Dimitra Gkika
Anna Rita Cantelmo
The Two-Way Relationship Between Calcium and Metabolism in Cancer
Frontiers in Cell and Developmental Biology
calcium
signaling
metabolism
interplay
cancer
title The Two-Way Relationship Between Calcium and Metabolism in Cancer
title_full The Two-Way Relationship Between Calcium and Metabolism in Cancer
title_fullStr The Two-Way Relationship Between Calcium and Metabolism in Cancer
title_full_unstemmed The Two-Way Relationship Between Calcium and Metabolism in Cancer
title_short The Two-Way Relationship Between Calcium and Metabolism in Cancer
title_sort two way relationship between calcium and metabolism in cancer
topic calcium
signaling
metabolism
interplay
cancer
url https://www.frontiersin.org/articles/10.3389/fcell.2020.573747/full
work_keys_str_mv AT camilledejos thetwowayrelationshipbetweencalciumandmetabolismincancer
AT dimitragkika thetwowayrelationshipbetweencalciumandmetabolismincancer
AT dimitragkika thetwowayrelationshipbetweencalciumandmetabolismincancer
AT annaritacantelmo thetwowayrelationshipbetweencalciumandmetabolismincancer
AT camilledejos twowayrelationshipbetweencalciumandmetabolismincancer
AT dimitragkika twowayrelationshipbetweencalciumandmetabolismincancer
AT dimitragkika twowayrelationshipbetweencalciumandmetabolismincancer
AT annaritacantelmo twowayrelationshipbetweencalciumandmetabolismincancer