Cancer-Related Increases and Decreases in Calcium Signaling at the Endoplasmic Reticulum-Mitochondria Interface (MAMs)

Danese, Alberto; Marchi, Saverio; Vitto, Veronica Angela Maria; Modesti, Lorenzo; Leo, Sara; Wieckowski, Mariusz R.; Giorgi, Carlotta; Pinton, Paolo

doi:10.1007/112_2020_43

Cited by 13 publications

(9 citation statements)

References 246 publications

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“…In addition to the extracellular-driven intrinsic pathway, an intracellular, mitochondria-centered pathway is activated in apoptosis, with the function of coupling insurmountable mitochondrial stress to cell death. Nevertheless, a wide number of stress conditions, including hypoxia, alteration, or poisoning of the electron transfer chain, unbuffered ROS production, and imbalanced mitochondrial protein homeostasis, can initiate mitochondrial permeability transition (MPT) [52,53]. MPT, followed by mitochondrial osmotic imbalance and mitochondrial outer membrane permeabilization, allows the release of several mitochondrial proteins, such as cytochrome C (cyt-C).…”

Section: Role Of Ca 2+ In Apoptosis and Cancermentioning

confidence: 99%

Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

Patergnani

Danese

Bouhamida

et al. 2020

IJMS

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185

128

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Calcium (Ca2+) is a major second messenger in cells and is essential for the fate and survival of all higher organisms. Different Ca2+ channels, pumps, or exchangers regulate variations in the duration and levels of intracellular Ca2+, which may be transient or sustained. These changes are then decoded by an elaborate toolkit of Ca2+-sensors, which translate Ca2+ signal to intracellular operational cell machinery, thereby regulating numerous Ca2+-dependent physiological processes. Alterations to Ca2+ homoeostasis and signaling are often deleterious and are associated with certain pathological states, including cancer. Altered Ca2+ transmission has been implicated in a variety of processes fundamental for the uncontrolled proliferation and invasiveness of tumor cells and other processes important for cancer progression, such as the development of resistance to cancer therapies. Here, we review what is known about Ca2+ signaling and how this fundamental second messenger regulates life and death decisions in the context of cancer, with particular attention directed to cell proliferation, apoptosis, and autophagy. We also explore the intersections of Ca2+ and the therapeutic targeting of cancer cells, summarizing the therapeutic opportunities for Ca2+ signal modulators to improve the effectiveness of current anticancer therapies.

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Section: Role Of Ca 2+ In Apoptosis and Cancermentioning

confidence: 99%

Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

Patergnani

Danese

Bouhamida

et al. 2020

IJMS

Self Cite

185

128

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show abstract

“…During apoptosis, an interaction between mitochondria and the ER involves the fusion of these two organelles, and the resulting regions are called mitochondria-associated ER membranes (MAMs). MAMs participate in the coordination of Ca 2+ signal transduction, triggering apoptosis ( 39 , 40 ). TRAP1 exerts dual regulatory effects on the mitochondrial apoptotic pathway ( Figure 1 ).…”

Section: Roles Of Trap1 In Apoptosis Resistancementioning

confidence: 99%

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

et al. 2021

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Tumor necrosis factor receptor-associated protein 1 (TRAP1), a member of the heat shock protein 90 (Hsp90) chaperone family, protects cells against oxidative stress and maintains mitochondrial integrity. To date, numerous studies have focused on understanding the relationship between aberrant TRAP1 expression and tumorigenesis. Mitochondrial TRAP1 is a key regulatory factor involved in metabolic reprogramming in tumor cells that favors the metabolic switch of tumor cells toward the Warburg phenotype. In addition, TRAP1 is involved in dual regulation of the mitochondrial apoptotic pathway and exerts an antiapoptotic effect on tumor cells. Furthermore, TRAP1 is involved in many cellular pathways by disrupting the cell cycle, increasing cell motility, and promoting tumor cell invasion and metastasis. Thus, TRAP1 is a very important therapeutic target, and treatment with TRAP1 inhibitors combined with chemotherapeutic agents may become a new therapeutic strategy for cancer. This review discusses the molecular mechanisms by which TRAP1 regulates tumor progression, considers its role in apoptosis, and summarizes recent advances in the development of selective, targeted TRAP1 and Hsp90 inhibitors.

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“…In recent years, there has been growing interest regarding mitochondria as potential crucial targets for cancer therapy [ 21 ], mainly because mitochondria can rapidly adapt to stressful conditions to permit cell survival. In fact, mitochondria are involved in metabolic changes and survival pathways regulating the oxidative stress response, mitochondrial plasticity, known as mitochondrial dynamics (mitochondrial fusion, mitochondrial fission, mitochondrial transfer, mitophagy) and Ca 2+ homeostasis [ 22 , 23 , 24 , 25 , 26 , 27 ], as they are the site where all these processes are often strictly intertwined.…”

Section: Introductionmentioning

confidence: 99%

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

Genovese

Carinci

Modesti

et al. 2021

IJMS

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Mitochondria are key regulators of cell survival and are involved in a plethora of mechanisms, such as metabolism, Ca2+ signaling, reactive oxygen species (ROS) production, mitophagy and mitochondrial transfer, fusion, and fission (known as mitochondrial dynamics). The tuning of these processes in pathophysiological conditions is fundamental to the balance between cell death and survival. Indeed, ROS overproduction and mitochondrial Ca2+ overload are linked to the induction of apoptosis, while the impairment of mitochondrial dynamics and metabolism can have a double-faceted role in the decision between cell survival and death. Tumorigenesis involves an intricate series of cellular impairments not yet completely clarified, and a further level of complexity is added by the onset of apoptosis resistance mechanisms in cancer cells. In the majority of cases, cancer relapse or lack of responsiveness is related to the emergence of chemoresistance, which may be due to the cooperation of several cellular protection mechanisms, often mitochondria-related. With this review, we aim to critically report the current evidence on the relationship between mitochondria and cancer chemoresistance with a particular focus on the involvement of mitochondrial dynamics, mitochondrial Ca2+ signaling, oxidative stress, and metabolism to possibly identify new approaches or targets for overcoming cancer resistance.

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Cancer-Related Increases and Decreases in Calcium Signaling at the Endoplasmic Reticulum-Mitochondria Interface (MAMs)

Cited by 13 publications

References 246 publications

Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

Various Aspects of Calcium Signaling in the Regulation of Apoptosis, Autophagy, Cell Proliferation, and Cancer

The Mitochondrial Chaperone TRAP1 as a Candidate Target of Oncotherapy

Mitochondria: Insights into Crucial Features to Overcome Cancer Chemoresistance

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