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  1. Article: Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma.

    Schnipper, Julie / Dhennin-Duthille, Isabelle / Ahidouch, Ahmed / Ouadid-Ahidouch, Halima

    Frontiers in pharmacology

    2020  Volume 11, Page(s) 568993

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer-related deaths in United States and Europe. It is predicted that PDAC will become the second leading cause of cancer-related deaths during the next decades. The development ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer-related deaths in United States and Europe. It is predicted that PDAC will become the second leading cause of cancer-related deaths during the next decades. The development of PDAC is not well understood, however, studies have shown that dysregulated exocrine pancreatic fluid secretion can contribute to pathologies of exocrine pancreas, including PDAC. The major roles of healthy exocrine pancreatic tissue are secretion of enzymes and bicarbonate rich fluid, where ion channels participate to fine-tune these biological processes. It is well known that ion channels located in the plasma membrane regulate multiple cellular functions and are involved in the communication between extracellular events and intracellular signaling pathways and can function as signal transducers themselves. Hereby, they contribute to maintain resting membrane potential, electrical signaling in excitable cells, and ion homeostasis. Despite their contribution to basic cellular processes, ion channels are also involved in the malignant transformation from a normal to a malignant phenotype. Aberrant expression and activity of ion channels have an impact on essentially all hallmarks of cancer defined as; uncontrolled proliferation, evasion of apoptosis, sustained angiogenesis and promotion of invasion and migration. Research indicates that certain ion channels are involved in the aberrant tumor growth and metastatic processes of PDAC. The purpose of this review is to summarize the important expression, localization, and function of ion channels in normal exocrine pancreatic tissue and how they are involved in PDAC progression and development. As ion channels are suggested to be potential targets of treatment they are furthermore suggested to be biomarkers of different cancers. Therefore, we describe the importance of ion channels in PDAC as markers of diagnosis and clinical factors.
    Language English
    Publishing date 2020-10-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.568993
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Orai1 Channel Regulates Human-Activated Pancreatic Stellate Cell Proliferation and TGF

    Radoslavova, Silviya / Folcher, Antoine / Lefebvre, Thibaut / Kondratska, Kateryna / Guénin, Stéphanie / Dhennin-Duthille, Isabelle / Gautier, Mathieu / Prevarskaya, Natalia / Ouadid-Ahidouch, Halima

    Cancers

    2021  Volume 13, Issue 10

    Abstract: Activated pancreatic stellate cells (aPSCs), the crucial mediator of pancreatic desmoplasia, are characterized, among others, by high proliferative potential and abundant transforming growth ... ...

    Abstract Activated pancreatic stellate cells (aPSCs), the crucial mediator of pancreatic desmoplasia, are characterized, among others, by high proliferative potential and abundant transforming growth factor
    Language English
    Publishing date 2021-05-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers13102395
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: TRPM7 Modulates Human Pancreatic Stellate Cell Activation.

    Auwercx, Julie / Kischel, Philippe / Lefebvre, Thibaut / Jonckheere, Nicolas / Vanlaeys, Alison / Guénin, Stéphanie / Radoslavova, Silviya / Van Seuningen, Isabelle / Ouadid-Ahidouch, Halima / Kocher, Hemant M / Dhennin-Duthille, Isabelle / Gautier, Mathieu

    Cells

    2022  Volume 11, Issue 14

    Abstract: Pancreatic diseases, such as pancreatitis or pancreatic ductal adenocarcinoma, are characterized by the presence of activated pancreatic stellate cells (PSCs). These cells represent key actors in the tumor stroma, as they actively participate in disease ... ...

    Abstract Pancreatic diseases, such as pancreatitis or pancreatic ductal adenocarcinoma, are characterized by the presence of activated pancreatic stellate cells (PSCs). These cells represent key actors in the tumor stroma, as they actively participate in disease development and progression: reprograming these PSCs into a quiescent phenotype has even been proposed as a promising strategy for restoring the hallmarks of a healthy pancreas. Since TRPM7 channels have been shown to regulate hepatic stellate cells proliferation and survival, we aimed to study the role of these magnesium channels in PSC activation and proliferation. PS-1 cells (isolated from a healthy pancreas) were used as a model of healthy PSCs: quiescence or activation were induced using all-trans retinoic acid or conditioned media of pancreatic cancer cells, respectively. The role of TRPM7 was studied by RNA silencing or by pharmacological inhibition. TRPM7 expression was found to be correlated with the activation status of PS-1 cells. TRPM7 expression was able to regulate proliferation through modulation of cell cycle regulators and most importantly p53, via the PI3K/Akt pathway, in a magnesium-dependent manner. Finally, the analysis of TCGA database showed the overexpression of TRPM7 in cancer-associated fibroblasts. Taken together, we provide strong evidences that TRPM7 can be considered as a marker of activated PSCs.
    MeSH term(s) Humans ; Magnesium/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatic Stellate Cells/pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Protein Serine-Threonine Kinases ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Pancreatic Neoplasms
    Chemical Substances TRPM Cation Channels ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2022-07-21
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11142255
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Mg

    Auwercx, Julie / Rybarczyk, Pierre / Kischel, Philippe / Dhennin-Duthille, Isabelle / Chatelain, Denis / Sevestre, Henri / Van Seuningen, Isabelle / Ouadid-Ahidouch, Halima / Jonckheere, Nicolas / Gautier, Mathieu

    Nutrients

    2021  Volume 13, Issue 1

    Abstract: Despite magnesium ( ... ...

    Abstract Despite magnesium (Mg
    MeSH term(s) Animals ; Biomarkers ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Disease Susceptibility ; Gastrointestinal Neoplasms/etiology ; Gastrointestinal Neoplasms/metabolism ; Gastrointestinal Neoplasms/mortality ; Gastrointestinal Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; Homeostasis ; Humans ; Ion Transport ; Magnesium/metabolism ; Protein Binding ; Signal Transduction
    Chemical Substances Biomarkers ; Cation Transport Proteins ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2021-01-13
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu13010210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: TRPM7 involvement in cancer: a potential prognostic factor.

    Dhennin-Duthille, Isabelle / Gautier, Mathieu / Korichneva, Irina / Ouadid-Ahidouch, Halima

    Magnesium research

    2014  Volume 27, Issue 3, Page(s) 103–112

    Abstract: Calcium (Ca(2+)) and magnesium (Mg(2+)) are important metal elements that regulate a variety of cellular processes such as proliferation, migration, and apoptosis, in cancer cells. Among the ionic channels mediating intracellular entry, the transient ... ...

    Abstract Calcium (Ca(2+)) and magnesium (Mg(2+)) are important metal elements that regulate a variety of cellular processes such as proliferation, migration, and apoptosis, in cancer cells. Among the ionic channels mediating intracellular entry, the transient receptor potential melastatin type 7 (TRPM7) channel is of particular interest, it being a non-selective, cationic channel mediating both Ca(2+) and Mg(2+) influx. TRPM7 is highly expressed in a number of human cancer tissues and cell lines. In this review, we summarise current knowledge on the physiological role of the dual function TRPM7 chanzyme, the potential application of TRPM7 as a diagnostic and prognostic marker of cancer progression with respect to clinical and pathological characteristics, and the molecular mechanisms implicated in cancerogenesis that specifically involve Ca(2+) and Mg(2+) influx through TRPM7 or kinase activity and interaction with cytoskeletal proteins.
    MeSH term(s) Animals ; Apoptosis/physiology ; Biomarkers, Tumor ; Calcium/metabolism ; Cell Differentiation/physiology ; Cell Division/physiology ; Cell Movement/physiology ; Embryonic Development/physiology ; Homeostasis ; Humans ; Ion Transport ; Magnesium/metabolism ; Mammals/metabolism ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/physiology ; Neoplasms/chemistry ; Neoplasms/mortality ; Prognosis ; Protein Processing, Post-Translational/physiology ; Protein Structure, Tertiary ; Protein-Serine-Threonine Kinases/chemistry ; Protein-Serine-Threonine Kinases/physiology ; Signal Transduction/physiology ; TRPM Cation Channels/chemistry ; TRPM Cation Channels/physiology
    Chemical Substances Biomarkers, Tumor ; Neoplasm Proteins ; TRPM Cation Channels ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2014-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1036384-1
    ISSN 1952-4021 ; 0953-1424
    ISSN (online) 1952-4021
    ISSN 0953-1424
    DOI 10.1684/mrh.2014.0367
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: TRPM6 is Essential for Magnesium Uptake and Epithelial Cell Function in the Colon.

    Luongo, Francesca / Pietropaolo, Giuseppe / Gautier, Mathieu / Dhennin-Duthille, Isabelle / Ouadid-Ahidouch, Halima / Wolf, Federica I / Trapani, Valentina

    Nutrients

    2018  Volume 10, Issue 6

    Abstract: Intestinal magnesium (Mg) uptake is essential for systemic Mg homeostasis. Colon cells express the two highly homologous transient receptor potential melastatin type (TRPM) 6 and 7 ... ...

    Abstract Intestinal magnesium (Mg) uptake is essential for systemic Mg homeostasis. Colon cells express the two highly homologous transient receptor potential melastatin type (TRPM) 6 and 7 Mg
    MeSH term(s) Cell Line, Tumor ; Colon/cytology ; Colon/metabolism ; Epithelial Cells/physiology ; Humans ; Intestinal Mucosa/cytology ; Magnesium/metabolism ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism
    Chemical Substances TRPM Cation Channels ; TRPM6 protein, human ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Magnesium (I38ZP9992A)
    Language English
    Publishing date 2018-06-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2518386-2
    ISSN 2072-6643 ; 2072-6643
    ISSN (online) 2072-6643
    ISSN 2072-6643
    DOI 10.3390/nu10060784
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: TRPM7/RPSA Complex Regulates Pancreatic Cancer Cell Migration.

    Lefebvre, Thibaut / Rybarczyk, Pierre / Bretaudeau, Clara / Vanlaeys, Alison / Cousin, Rémi / Brassart-Pasco, Sylvie / Chatelain, Denis / Dhennin-Duthille, Isabelle / Ouadid-Ahidouch, Halima / Brassart, Bertrand / Gautier, Mathieu

    Frontiers in cell and developmental biology

    2020  Volume 8, Page(s) 549

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with a very poor prognosis due to highly metastatic profile. Cell migration is an essential step of the metastatic cascade allowing cancer cells to spread toward target tissues. Recent studies strongly suggest that bioactive elastin peptides, also named elastokines or elastin-derived peptides (EDPs), are released in the extracellular microenvironment during tumoral remodeling of the stroma. EDPs stimulate cancer cell migration by interacting with their membrane receptor, ribosomal protein SA (RPSA). Others membrane proteins like ion channels are also involved in cancer cell migration. It has been recently shown that the transient receptor potential melastatin-related 7 (TRPM7) channel regulates PDAC cell migration and invasion. The objective of this work was to study the effect of EDPs on TRPM7 channel in human pancreatic cancer cells. We showed that EDPs promote MIA PaCa-2 cell migration using Boyden chamber assay. Cells transfected with a siRNA targeting TRPM7 were not able to migrate in response to EDPs indicating that TRPM7 regulated cell migration induced by these peptides. Moreover, EDPs were able to stimulate TRPM7 currents recorded by Patch-Clamp. Finally, we showed that TRPM7 channels and RPSA receptors are colocalized at the plasma membrane of human pancreatic cancer cells. Taken together, our data suggest that TRPM7/RPSA complex regulated human pancreatic cancer cell migration. This complex may be a promising therapeutic target in PDAC.
    Language English
    Publishing date 2020-07-08
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2020.00549
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Cadmium exposure enhances cell migration and invasion through modulated TRPM7 channel expression.

    Vanlaeys, Alison / Fouquet, Grégory / Kischel, Philippe / Hague, Frédéric / Pasco-Brassart, Sylvie / Lefebvre, Thibaut / Rybarczyk, Pierre / Dhennin-Duthille, Isabelle / Brassart, Bertrand / Ouadid-Ahidouch, Halima / Gautier, Mathieu

    Archives of toxicology

    2020  Volume 94, Issue 3, Page(s) 735–747

    Abstract: Cadmium is a xenobiotic involved in neoplastic transformation. Cadmium enters the cells through divalent cation transporters including the Transient Receptor Potential Melastatin-related 7 (TRPM7) which is known to be involved in cancer cell fate. This ... ...

    Abstract Cadmium is a xenobiotic involved in neoplastic transformation. Cadmium enters the cells through divalent cation transporters including the Transient Receptor Potential Melastatin-related 7 (TRPM7) which is known to be involved in cancer cell fate. This work aimed to study the role of TRPM7 in neoplastic transformation induced by cadmium exposure in non-cancer epithelial cells. Non-cancer epithelial cells were chronically exposed to low-dose of cadmium. TRPM7 expression and function were studied by Western-Blot, Patch-Clamp and calcium and magnesium imaging. Finally, cell migration and invasion were studied by Boyden chamber assays. Chronic cadmium exposure induced TRPM7 overexpression and increased the membrane currents (P < 0.001). Cells exposed to cadmium had higher intracellular calcium and magnesium levels (P < 0.05). TRPM7 silencing restored calcium levels but strongly decreased intracellular magnesium concentration (P < 0.001). Moreover, cadmium exposure enhanced both cell migration and invasion, but TRPM7 silencing strongly decreased these features (P < 0.001). Furthermore, mammary epithelial cells exposed to cadmium became rounded and had less cell-to-cell junctions. Cadmium exposure decreased epithelial markers while the mesenchymal ones were increased. Importantly, TRPM7 silencing was able to reverse these phenotypic modifications (P < 0.05). To summarize, our data show that chronic cadmium exposure enhanced TRPM7 expression and activity in non-cancer epithelial cells. TRPM7 overexpression induced intracellular magnesium increase and stimulated cell migration and invasion. These neoplastic properties could be linked to a TRPM7-dependent epithelial-to-mesenchymal transition reprogramming in cell exposed to cadmium. These findings provide new insights into the regulation of cell fates by cadmium exposure.
    MeSH term(s) Cadmium/toxicity ; Cell Movement/drug effects ; Epithelial-Mesenchymal Transition ; Hazardous Substances/toxicity ; Humans ; TRPM Cation Channels/metabolism
    Chemical Substances Hazardous Substances ; TRPM Cation Channels ; Cadmium (00BH33GNGH)
    Language English
    Publishing date 2020-02-20
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 124992-7
    ISSN 1432-0738 ; 0340-5761
    ISSN (online) 1432-0738
    ISSN 0340-5761
    DOI 10.1007/s00204-020-02674-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The Transient Receptor Potential Melastatin 7 Channel Regulates Pancreatic Cancer Cell Invasion through the Hsp90α/uPA/MMP2 pathway.

    Rybarczyk, Pierre / Vanlaeys, Alison / Brassart, Bertrand / Dhennin-Duthille, Isabelle / Chatelain, Denis / Sevestre, Henri / Ouadid-Ahidouch, Halima / Gautier, Mathieu

    Neoplasia (New York, N.Y.)

    2017  Volume 19, Issue 4, Page(s) 288–300

    Abstract: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis. There is an urgent need to better understand the molecular mechanisms that regulate PDAC cell aggressiveness. The transient receptor potential melastatin 7 ( ... ...

    Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a very poor prognosis. There is an urgent need to better understand the molecular mechanisms that regulate PDAC cell aggressiveness. The transient receptor potential melastatin 7 (TRPM7) is a nonselective cationic channel that mainly conducts Ca
    MeSH term(s) Calcium/metabolism ; Cell Line, Tumor ; Gene Expression ; Gene Silencing ; HSP90 Heat-Shock Proteins/metabolism ; Humans ; Lymphatic Metastasis ; Magnesium/metabolism ; Matrix Metalloproteinase 2/metabolism ; Models, Biological ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics ; Protein-Serine-Threonine Kinases/metabolism ; Proteolysis ; Signal Transduction ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Urokinase-Type Plasminogen Activator/metabolism
    Chemical Substances HSP90 Heat-Shock Proteins ; HSP90AA2P protein, human ; TRPM Cation Channels ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1) ; Urokinase-Type Plasminogen Activator (EC 3.4.21.73) ; Matrix Metalloproteinase 2 (EC 3.4.24.24) ; Magnesium (I38ZP9992A) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2017-03-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2017.01.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Ion Channels: New Actors Playing in Chemotherapeutic Resistance.

    Kischel, Philippe / Girault, Alban / Rodat-Despoix, Lise / Chamlali, Mohamed / Radoslavova, Silviya / Abou Daya, Hiba / Lefebvre, Thibaut / Foulon, Arthur / Rybarczyk, Pierre / Hague, Frédéric / Dhennin-Duthille, Isabelle / Gautier, Mathieu / Ouadid-Ahidouch, Halima

    Cancers

    2019  Volume 11, Issue 3

    Abstract: In the battle against cancer cells, therapeutic modalities are drastically limited by intrinsic or acquired drug resistance. Resistance to therapy is not only common, but expected: if systemic agents used for cancer treatment are usually active at the ... ...

    Abstract In the battle against cancer cells, therapeutic modalities are drastically limited by intrinsic or acquired drug resistance. Resistance to therapy is not only common, but expected: if systemic agents used for cancer treatment are usually active at the beginning of therapy (i.e., 90% of primary breast cancers and 50% of metastases), about 30% of patients with early-stage breast cancer will have recurrent disease. Altered expression of ion channels is now considered as one of the hallmarks of cancer, and several ion channels have been linked to cancer cell resistance. While ion channels have been associated with cell death, apoptosis and even chemoresistance since the late 80s, the molecular mechanisms linking ion channel expression and/or function with chemotherapy have mostly emerged in the last ten years. In this review, we will highlight the relationships between ion channels and resistance to chemotherapy, with a special emphasis on the underlying molecular mechanisms.
    Language English
    Publishing date 2019-03-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers11030376
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