Novel frontiers in calcium signaling: A possible target for chemotherapy

Bonora, Massimo; Giorgi, Carlotta; Pinton, Paolo

doi:10.1016/j.phrs.2015.05.008

Cited by 20 publications

(20 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The major findings of this study are that (i) venetoclax (ABT-199) does not dysregulate This is in contrast to several other stress inducers, including apoptotic stimuli like ceramide and chemotherapeutic/anti-cancer drugs [42,43]. Recently, fast and constitutive changes in cytosolic Ca 2+ levels have been proposed as early markers for the detection of cytotoxicity in response to H 2 O 2 , staurosporin, As 2 O 3 , gossypol and titanium(IV)-salane complexes in different cancer cell models [44].…”

Section: Discussionmentioning

confidence: 84%

“…Moreover, in cisplatin-resistant ovarian cancer cells, ABT-737 can also promote the formation of ERmitochondrial contact sites induced by cisplatin, thereby augmenting cisplatin-induced Ca 2+ rise in the mitochondria and apoptosis [38]. These observations further underpin the intimate link between the effective response to anti-cancer therapeutics and efficient ER-mitochondrial Ca 2+ transfer [43,46,49].…”

Section: Discussionmentioning

confidence: 90%

See 1 more Smart Citation

The selective Bcl-2 inhibitor venetoclax, a BH3 mimetic, does not dysregulate intracellular Ca 2+ signaling

Vervloessem

Ivanova

Luyten

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 90%

The selective Bcl-2 inhibitor venetoclax, a BH3 mimetic, does not dysregulate intracellular Ca 2+ signaling

Vervloessem

Ivanova

Luyten

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

View full text Add to dashboard Cite

show abstract

“…The major intracellular Ca 2+ storage unit is the ER (luminal [Ca 2+ ] ER 500 μM-1 mM)3, which exhibits significant heterogeneity in the Ca 2+ level among its sub-regions. Upon stimulation with agonists such as histamine or ATP, the ER rapidly releases Ca 2+ through the inositol 1,4,5-trisphosphate receptor (IP3R), thereby generating transient waves in the cytoplasm and mitochondria to promote cell activities45. Upon ER Ca 2+ depletion, the luminal sensor protein STIM1 oligomerizes on the ER membrane and migrates to sites of ER/PM interaction to activate the highly Ca 2+ -selective ORAI channels located on the PM67.…”

mentioning

confidence: 99%

TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry

Sbano

Bonora

Marchi

et al. 2017

Sci Rep

Self Cite

View full text Add to dashboard Cite

Lysosomes are membrane-bound organelles mainly involved in catabolic processes. In addition, lysosomes can expel their contents outside of the cell via lysosomal exocytosis. Some of the key steps involved in these important cellular processes, such as vesicular fusion and trafficking, require calcium (Ca2+) signaling. Recent data show that lysosomal functions are transcriptionally regulated by transcription factor EB (TFEB) through the induction of genes involved in lysosomal biogenesis and exocytosis. Given these observations, we investigated the roles of TFEB and lysosomes in intracellular Ca2+ homeostasis. We studied the effect of transient modulation of TFEB expression in HeLa cells by measuring the cytosolic Ca2+ response after capacitative Ca2+ entry activation and Ca2+ dynamics in the endoplasmic reticulum (ER) and directly in lysosomes. Our observations show that transient TFEB overexpression significantly reduces cytosolic Ca2+ levels under a capacitative influx model and ER re-uptake of calcium, increasing the lysosomal Ca2+ buffering capacity. Moreover, lysosomal destruction or damage abolishes these TFEB-dependent effects in both the cytosol and ER. These results suggest a possible Ca2+ buffering role for lysosomes and shed new light on lysosomal functions during intracellular Ca2+ homeostasis.

show abstract

“…Many cell death-inducing agents, like H 2 O 2 (86, 87), arachidonic acid (88), ceramide (50, 86), and menadione (89, 90) have been shown to act at the ER by triggering Ca 2+ release through IP 3 Rs and subsequently provoking mitochondrial Ca 2+ rises (91). Moreover, the ability of chemotherapeutics, like adriamycin (77), arsenic trioxide (71), and mitotane (82) and of photodynamic therapy (78) to kill cancer cells strongly depends on their ability to adequately induce ER–mitochondrial Ca 2+ transfer (92). The spectrum of chemotherapeutics acting in this way might be quite broad, since recently it was shown that cisplatin and topotecan increase [Ca 2+ ] cyt over time, although [Ca 2+ ] mt was not determined (93).…”

Section: Mitochondrial Ca2+ Signals As Regulators Of Cell Death and Smentioning

confidence: 99%

“…Moreover, FATE1 expression is also inversely correlated with the overall survival of adrenocortical cancer patients (82). Oppositely, enhancing ER–mitochondrial Ca 2+ transfer will favor cell-death therapies (92). Interestingly, some anticancer drugs might actually impact ER–mitochondrial contact sites and thereby enhance the response to other chemotherapeutics.…”

Section: Er–mitochondrial Ca2+ Signaling Underlying Cellular Senescenmentioning

confidence: 99%

Endoplasmic Reticulum–Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival

et al. 2017

View full text Add to dashboard Cite

Calcium ions (Ca2+) are crucial, ubiquitous, intracellular second messengers required for functional mitochondrial metabolism during uncontrolled proliferation of cancer cells. The mitochondria and the endoplasmic reticulum (ER) are connected via “mitochondria-associated ER membranes” (MAMs) where ER–mitochondria Ca2+ transfer occurs, impacting the mitochondrial biology related to several aspects of cellular survival, autophagy, metabolism, cell death sensitivity, and metastasis, all cancer hallmarks. Cancer cells appear addicted to these constitutive ER–mitochondrial Ca2+ fluxes for their survival, since they drive the tricarboxylic acid cycle and the production of mitochondrial substrates needed for nucleoside synthesis and proper cell cycle progression. In addition to this, the mitochondrial Ca2+ uniporter and mitochondrial Ca2+ have been linked to hypoxia-inducible factor 1α signaling, enabling metastasis and invasion processes, but they can also contribute to cellular senescence induced by oncogenes and replication. Finally, proper ER–mitochondrial Ca2+ transfer seems to be a key event in the cell death response of cancer cells exposed to chemotherapeutics. In this review, we discuss the emerging role of ER–mitochondrial Ca2+ fluxes underlying these cancer-related features.

show abstract

Novel frontiers in calcium signaling: A possible target for chemotherapy

Cited by 20 publications

References 28 publications

The selective Bcl-2 inhibitor venetoclax, a BH3 mimetic, does not dysregulate intracellular Ca 2+ signaling

The selective Bcl-2 inhibitor venetoclax, a BH3 mimetic, does not dysregulate intracellular Ca 2+ signaling

TFEB-mediated increase in peripheral lysosomes regulates store-operated calcium entry

Endoplasmic Reticulum–Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival

Contact Info

Product

Resources

About