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Article: Store operated calcium channels in cancer progression.

Shapovalov, George / Gordienko, Dmitri / Prevarskaya, Natalia

International review of cell and molecular biology

2021 Volume 363, Page(s) 123–168

Abstract: In recent decades cancer emerged as one of the leading causes of death in the developed countries, with some types of cancer contributing to the top 10 causes of death on the list of the World Health Organization. Carcinogenesis, a malignant ... ...

Abstract	In recent decades cancer emerged as one of the leading causes of death in the developed countries, with some types of cancer contributing to the top 10 causes of death on the list of the World Health Organization. Carcinogenesis, a malignant transformation causing formation of tumors in normal tissues, is associated with changes in the cell cycle caused by suppression of signaling pathways leading to cell death and facilitation of those enhancing proliferation. Further progression of cancer, during which benign tumors acquire more aggressive phenotypes, is characterized by metastatic dissemination through the body driven by augmented motility and invasiveness of cancer cells. All these processes are associated with alterations in calcium homeostasis in cancer cells, which promote their proliferation, motility and invasion, and dissuade cell death or cell cycle arrest. Remodeling of store-operated calcium entry (SOCE), one of the major pathways regulating intracellular Ca
MeSH term(s)	Animals ; Calcium/metabolism ; Calcium Channels/metabolism ; Carcinogenesis/metabolism ; Humans ; Neoplasms/metabolism ; Neoplasms/pathology
Chemical Substances	Calcium Channels ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-03-30
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2427220-6
ISSN	1937-6448 ; 0074-7696
ISSN	1937-6448 ; 0074-7696
DOI	10.1016/bs.ircmb.2021.02.016
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Article: TRPV6 Calcium Channel Targeting by Antibodies Raised against Extracellular Epitopes Induces Prostate Cancer Cell Apoptosis.

Haustrate, Aurélien / Shapovalov, George / Spriet, Corentin / Cordier, Clément / Kondratskyi, Artem / Noyer, Lucile / Foulquier, François / Prevarskaya, Natalia / Lehen'kyi, V'yacheslav

Cancers

2023 Volume 15, Issue 6

Abstract: The TRPV6 calcium channel is known to be up-regulated in various tumors. The efforts to target the TRPV6 channel in vivo are still ongoing to propose an effective therapy against cancer. Here, we report the generation of two antibodies raised against ... ...

Abstract	The TRPV6 calcium channel is known to be up-regulated in various tumors. The efforts to target the TRPV6 channel in vivo are still ongoing to propose an effective therapy against cancer. Here, we report the generation of two antibodies raised against extracellular epitopes corresponding to the extracellular loop between S1 and S2 (rb79) and the pore region (rb82). These antibodies generated a complex biphasic response with the transient activation of the TRPV6 channel. Store-operated calcium entry was consequently potentiated in the prostate cancer cell line LNCaP upon the treatment. Both rb79 and rb82 antibodies significantly decreased cell survival rate in a dose-dependent manner as compared to the control antibodies of the same isotype. This decrease was due to the enhanced cell death via apoptosis revealed using a sub-G1 peak in a cell cycle assay, TUNEL assay, and a Hoechst staining, having no effects in the PC3M
Language	English
Publishing date	2023-03-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15061825
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Article: Metabolic Disorders and Cancer: Store-Operated Ca

Ritaine, Abigaël / Shapovalov, George / Prevarskaya, Natalia

Advances in experimental medicine and biology

2017 Volume 993, Page(s) 623–637

Abstract: Store-operated calcium entry (SOCE) plays important roles in a multitude of cellular processes, from muscle contraction to cellular proliferation and migration. Dysregulation of SOCE is responsible for the advancement of multiple diseases, ranging from ... ...

Abstract	Store-operated calcium entry (SOCE) plays important roles in a multitude of cellular processes, from muscle contraction to cellular proliferation and migration. Dysregulation of SOCE is responsible for the advancement of multiple diseases, ranging from immune diseases, myopathies, to terminal ones like cancer. Naturally, SOCE has been a focus of many studies and review papers which, however, primarily concentrated on the principal players localized to the plasma membrane and responsible for Ca
Language	English
Publishing date	2017
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-3-319-57732-6_31
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Article ; Online: Role of TRP ion channels in cancer and tumorigenesis.

Shapovalov, George / Ritaine, Abigael / Skryma, Roman / Prevarskaya, Natalia

Seminars in immunopathology

2016 Volume 38, Issue 3, Page(s) 357–369

Abstract: Transient receptor potential (TRP) channels are recently identified proteins that form a versatile family of ion channels, the majority of which are calcium permeable and exhibit complex regulatory patterns with sensitivity to multiple environmental ... ...

Abstract	Transient receptor potential (TRP) channels are recently identified proteins that form a versatile family of ion channels, the majority of which are calcium permeable and exhibit complex regulatory patterns with sensitivity to multiple environmental factors. While this sensitivity has captured early attention, leading to recognition of TRP channels as environmental and chemical sensors, many later studies concentrated on the regulation of intracellular calcium by TRP channels. Due to mutations, dysregulation of ion channel gating or expression levels, normal spatiotemporal patterns of local Ca(2+) distribution become distorted. This causes deregulation of downstream effectors sensitive to changes in Ca(2+) homeostasis that, in turn, promotes pathophysiological cancer hallmarks, such as enhanced survival, proliferation and invasion. These observations give rise to the appreciation of the important contributions that TRP channels make to many cellular processes controlling cell fate and positioning these channels as important players in cancer regulation. This review discusses the accumulated scientific knowledge focused on TRP channel involvement in regulation of cell fate in various transformed tissues.
MeSH term(s)	Animals ; Apoptosis/genetics ; Calcium/metabolism ; Cell Movement/genetics ; Cell Proliferation ; Cell Transformation, Neoplastic/genetics ; Cell Transformation, Neoplastic/metabolism ; Gene Expression ; Humans ; Multigene Family ; Neoplasms/etiology ; Neoplasms/metabolism ; Neoplasms/pathology ; Signal Transduction ; Transient Receptor Potential Channels/genetics ; Transient Receptor Potential Channels/metabolism
Chemical Substances	Transient Receptor Potential Channels ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2016-05
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-015-0525-1
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Article ; Online: Allosteric cross-talk between the hydrophobic cleft and the BH4 domain of Bcl-2 in control of inositol 1,4,5-trisphosphate receptor activity.

Shapovalov, George / Ritaine, Abigaël / Essonghe, Nadege Charlene / de Ridder, Ian / Ivanova, Hristina / Karamanou, Spyridoula / Economou, Anastassios / Bultynck, Geert / Skryma, Roman / Prevarskaya, Natalia

Exploration of targeted anti-tumor therapy

2022 Volume 3, Issue 3, Page(s) 375–391

Abstract: Aim: Inositol 1,4,5-trisphosphate receptor (IP: Methods: Organelle membrane-derived (OMD) patch-clamp and circular dichroism (CD) thermal melting experiments were used to elucidate the effects of the ABT-199 (venetoclax) on the IP: Results: It was ...

Abstract	Aim: Inositol 1,4,5-trisphosphate receptor (IP Methods: Organelle membrane-derived (OMD) patch-clamp and circular dichroism (CD) thermal melting experiments were used to elucidate the effects of the ABT-199 (venetoclax) on the IP Results: It was shown that occlusion of Bcl-2's hydrophobic cleft by the drug ABT-199 finely modulates IP Conclusions: Bcl-2 is an important regulator of IP
Language	English
Publishing date	2022-06-28
Publishing country	United States
Document type	Journal Article
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2022.00088
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Article ; Online: Use of 2,6-diaminopurine as a potent suppressor of UGA premature stop codons in cystic fibrosis.

Leroy, Catherine / Spelier, Sacha / Essonghe, Nadège Charlene / Poix, Virginie / Kong, Rebekah / Gizzi, Patrick / Bourban, Claire / Amand, Séverine / Bailly, Christine / Guilbert, Romain / Hannebique, David / Persoons, Philippe / Arhant, Gwenaëlle / Prévotat, Anne / Reix, Philippe / Hubert, Dominique / Gérardin, Michèle / Chamaillard, Mathias / Prevarskaya, Natalia /

Rebuffat, Sylvie / Shapovalov, George / Beekman, Jeffrey / Lejeune, Fabrice

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 4, Page(s) 970–985

Abstract: Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can ... ...

Abstract	Nonsense mutations are responsible for around 10% of cases of genetic diseases, including cystic fibrosis. 2,6-diaminopurine (DAP) has recently been shown to promote efficient readthrough of UGA premature stop codons. In this study, we show that DAP can correct a nonsense mutation in the Cftr gene in vivo in a new CF mouse model, in utero, and through breastfeeding, thanks, notably, to adequate pharmacokinetic properties. DAP turns out to be very stable in plasma and is distributed throughout the body. The ability of DAP to correct various endogenous UGA nonsense mutations in the CFTR gene and to restore its function in mice, in organoids derived from murine or patient cells, and in cells from patients with cystic fibrosis reveals the potential of such readthrough-stimulating molecules in developing a therapeutic approach. The fact that correction by DAP of certain nonsense mutations reaches a clinically relevant level, as judged from previous studies, makes the use of this compound all the more attractive.
MeSH term(s)	Mice ; Animals ; Codon, Nonsense ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis/genetics ; Codon, Terminator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics
Chemical Substances	Codon, Nonsense ; Codon, Terminator ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; 2,6-diaminopurine (49P95BAU4Z)
Language	English
Publishing date	2023-01-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.01.014
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Article ; Online: Calcium channels and prostate cancer.

Shapovalov, George / Skryma, Roman / Prevarskaya, Natalia

Recent patents on anti-cancer drug discovery

2012 Volume 8, Issue 1, Page(s) 18–26

Abstract: Calcium channels significantly contribute to many cellular processes, including such critical ones as proliferation, differentiation, and apoptosis. In prostate cancer, the influence of calcium channels has been known for over 30 years, with the first ... ...

Abstract	Calcium channels significantly contribute to many cellular processes, including such critical ones as proliferation, differentiation, and apoptosis. In prostate cancer, the influence of calcium channels has been known for over 30 years, with the first observations that calcium channel blockers affect the progression of cancer towards more aggressive phase. Later research identified additional classes of channel proteins having an important regulatory role and affecting malignant transformation. This review discusses the accumulated scientific knowledge focused on calcium channel involvement in regulation of cell fate in prostate tissues as well as recent developments in patents targeted at prostate cancer treatments and involving calcium channel modulators.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Calcium Channel Blockers/chemistry ; Calcium Channel Blockers/pharmacology ; Calcium Channels/drug effects ; Calcium Channels/metabolism ; Cell Cycle/drug effects ; Cell Proliferation/drug effects ; Drug Design ; Humans ; Legislation, Drug ; Male ; Patents as Topic ; Prostatic Neoplasms/drug therapy ; Prostatic Neoplasms/metabolism ; Prostatic Neoplasms/pathology
Chemical Substances	Antineoplastic Agents ; Calcium Channel Blockers ; Calcium Channels
Language	English
Publishing date	2012-06-11
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2250820-X
ISSN	2212-3970 ; 1574-8928
ISSN (online)	2212-3970
ISSN	1574-8928
DOI	10.2174/15748928130103
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Article ; Online: TRPC3 shapes the ER-mitochondria Ca

Farfariello, Valerio / Gordienko, Dmitri V / Mesilmany, Lina / Touil, Yasmine / Germain, Emmanuelle / Fliniaux, Ingrid / Desruelles, Emilie / Gkika, Dimitra / Roudbaraki, Morad / Shapovalov, George / Noyer, Lucile / Lebas, Mathilde / Allart, Laurent / Zienthal-Gelus, Nathalie / Iamshanova, Oksana / Bonardi, Franck / Figeac, Martin / Laine, William / Kluza, Jerome /

Marchetti, Philippe / Quesnel, Bruno / Metzger, Daniel / Bernard, David / Parys, Jan B / Lemonnier, Loïc / Prevarskaya, Natalia

Nature communications

2022 Volume 13, Issue 1, Page(s) 956

Abstract: Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering ... ...

Abstract	Cellular senescence is implicated in a great number of diseases including cancer. Although alterations in mitochondrial metabolism were reported as senescence drivers, the underlying mechanisms remain elusive. We report the mechanism altering mitochondrial function and OXPHOS in stress-induced senescent fibroblasts. We demonstrate that TRPC3 protein, acting as a controller of mitochondrial Ca
MeSH term(s)	Calcium/metabolism ; Carcinogenesis/pathology ; Cell Line, Tumor ; Cell Proliferation ; Cellular Senescence ; Endoplasmic Reticulum/metabolism ; HEK293 Cells ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism ; Mitochondria/metabolism ; Neoplasms/pathology ; Oxidative Phosphorylation ; Primary Cell Culture ; TRPC Cation Channels/metabolism
Chemical Substances	Inositol 1,4,5-Trisphosphate Receptors ; TRPC Cation Channels ; TRPC3 cation channel ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-02-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-28597-x
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Article: Functional and physiopathological implications of TRP channels.

Smani, Tarik / Shapovalov, George / Skryma, Roman / Prevarskaya, Natalia / Rosado, Juan A

Biochimica et biophysica acta

2015 Volume 1853, Issue 8, Page(s) 1772–1782

Abstract: Transient Receptor Potential (TRP) channel proteins are a diverse family of proteins that are expressed in many organisms, tissues and cell types. TRP channels respond to a variety of stimuli, including light, mechanical or chemical stimuli, temperature, ...

Abstract	Transient Receptor Potential (TRP) channel proteins are a diverse family of proteins that are expressed in many organisms, tissues and cell types. TRP channels respond to a variety of stimuli, including light, mechanical or chemical stimuli, temperature, pH or osmolarity. In addition, several TRP family members have been identified as downstream molecules in the G protein-coupled receptor signaling pathway. TRP proteins are involved in a variety of cell functions both in non-excitable and excitable cells due to their diverse permeability to cations and their ability to modulate intracellular Ca2+ signaling. Emerging evidence suggests that TRP channel dysfunction significantly contributes to the physiopathology of a number of diseases, including cardiovascular, neurological, metabolic or neoplastic disorders. This review focuses on the implication of TRP proteins in the pathogenesis of some of the most prevalent disorders in human. We summarize the current findings regarding the role of TRP proteins in the development of cardiovascular disease, diabetes mellitus as well as diabetic complications, and tumorigenesis and present TRP proteins as targets of potential diagnostic and therapeutic strategies.
MeSH term(s)	Animals ; Carcinogenesis/genetics ; Cardiovascular Diseases/genetics ; Cardiovascular Physiological Phenomena/genetics ; Channelopathies/complications ; Channelopathies/genetics ; Diabetes Mellitus/genetics ; Diabetes Mellitus/pathology ; Humans ; Transient Receptor Potential Channels/genetics ; Transient Receptor Potential Channels/physiology
Chemical Substances	Transient Receptor Potential Channels
Language	English
Publishing date	2015-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamcr.2015.04.016
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Article ; Online: NALCN-mediated sodium influx confers metastatic prostate cancer cell invasiveness.

Folcher, Antoine / Gordienko, Dmitri / Iamshanova, Oksana / Bokhobza, Alexandre / Shapovalov, George / Kannancheri-Puthooru, Dheeraj / Mariot, Pascal / Allart, Laurent / Desruelles, Emilie / Spriet, Corentin / Diez, Raquel / Oullier, Thibauld / Marionneau-Lambot, Séverine / Brisson, Lucie / Geraci, Sandra / Impheng, Hathaichanok / Lehen'kyi, V'yacheslav / Haustrate, Aurélien / Mihalache, Adriana /

Gosset, Pierre / Chadet, Stéphanie / Retif, Stéphanie / Laube, Maryline / Sobilo, Julien / Lerondel, Stéphanie / Villari, Giulia / Serini, Guido / Pla, Alessandra Fiorio / Roger, Sébastien / Fromont-Hankard, Gaelle / Djamgoz, Mustafa / Clezardin, Philippe / Monteil, Arnaud / Prevarskaya, Natalia

The EMBO journal

2023 Volume 42, Issue 13, Page(s) e112198

Abstract: There is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying ... ...

Abstract	There is growing evidence that ion channels are critically involved in cancer cell invasiveness and metastasis. However, the molecular mechanisms of ion signaling promoting cancer behavior are poorly understood and the complexity of the underlying remodeling during metastasis remains to be explored. Here, using a variety of in vitro and in vivo techniques, we show that metastatic prostate cancer cells acquire a specific Na
MeSH term(s)	Male ; Humans ; Sodium/metabolism ; Ion Channels/metabolism ; Ion Transport ; Prostatic Neoplasms ; Membrane Proteins/genetics ; Membrane Proteins/metabolism
Chemical Substances	Sodium (9NEZ333N27) ; Ion Channels ; NALCN protein, human ; Membrane Proteins
Language	English
Publishing date	2023-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	586044-1
ISSN	1460-2075 ; 0261-4189
ISSN (online)	1460-2075
ISSN	0261-4189
DOI	10.15252/embj.2022112198
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