Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination
Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> channels, composed of Orai1 and STIM1 (stromal interaction molecule 1) proteins, are the main Ca<sup>2+</sup> entry mechanism in lymphocytes. Their role in cell migration and metastasis is demonstrated in solid can...
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doaj-11baa3710d854422ab668bcbf15f0d892020-11-25T00:54:56ZengMDPI AGCancers2072-66942018-10-01101140210.3390/cancers10110402cancers10110402Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma DisseminationSimon Latour0Isabelle Mahouche1Floriane Cherrier2Lamia Azzi-Martin3Valérie Velasco4Pierre Soubeyran5Jean-Philippe Merlio6Sandrine Poglio7Laurence Bresson-Bepoldin8Department of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceInstitut Bergonié, Comprehensive Cancer Centre, F-33000 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceDepartment of Life and Health Sciences, University of Bordeaux, F-33076 Bordeaux, FranceCa<sup>2+</sup> release-activated Ca<sup>2+</sup> channels, composed of Orai1 and STIM1 (stromal interaction molecule 1) proteins, are the main Ca<sup>2+</sup> entry mechanism in lymphocytes. Their role in cell migration and metastasis is demonstrated in solid cancers but it remains elusive in malignant hemopathies. Diffuse large B cell lymphoma (DLBCL) is characterized by the dissemination of neoplastic B cells throughout the organism which is under the control of chemokines such as Stromal Derived Factor 1 (SDF-1) and its receptor CXCR4. CXCR4 activation triggers a complex intracellular signaling including an increase in intracellular Ca<sup>2+</sup> concentration whose role is still unclear. Using pharmacological and genetic approaches, we revealed that STIM1 and Orai1 were responsible for Ca<sup>2+</sup> influx induced by SDF-1. Furthermore, we provide in vitro and in vivo evidence that they are necessary for basal or SDF-1-induced DLBCL cell migration which is independent of Ca<sup>2+</sup> entry. We identify that they act as effectors coupling RhoA and ROCK dependent signaling pathway to MLC2 phosphorylation and actin polymerization. Finally, we revealed an alteration of Orai1 and STIM1 expression in extra-nodal DLBCL. Thus, we discovered a novel Ca<sup>2+</sup>-independent but Orai1 and STIM1-dependent signaling pathway involved in basal and CXCR4 dependent cell migration, which could be relevant for DLBCL physiopathology.https://www.mdpi.com/2072-6694/10/11/402Orai1STIM1calciummigrationlymphocytelymphoma |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Simon Latour Isabelle Mahouche Floriane Cherrier Lamia Azzi-Martin Valérie Velasco Pierre Soubeyran Jean-Philippe Merlio Sandrine Poglio Laurence Bresson-Bepoldin |
spellingShingle |
Simon Latour Isabelle Mahouche Floriane Cherrier Lamia Azzi-Martin Valérie Velasco Pierre Soubeyran Jean-Philippe Merlio Sandrine Poglio Laurence Bresson-Bepoldin Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination Cancers Orai1 STIM1 calcium migration lymphocyte lymphoma |
author_facet |
Simon Latour Isabelle Mahouche Floriane Cherrier Lamia Azzi-Martin Valérie Velasco Pierre Soubeyran Jean-Philippe Merlio Sandrine Poglio Laurence Bresson-Bepoldin |
author_sort |
Simon Latour |
title |
Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination |
title_short |
Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination |
title_full |
Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination |
title_fullStr |
Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination |
title_full_unstemmed |
Calcium Independent Effect of Orai1 and STIM1 in Non-Hodgkin B Cell Lymphoma Dissemination |
title_sort |
calcium independent effect of orai1 and stim1 in non-hodgkin b cell lymphoma dissemination |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2018-10-01 |
description |
Ca<sup>2+</sup> release-activated Ca<sup>2+</sup> channels, composed of Orai1 and STIM1 (stromal interaction molecule 1) proteins, are the main Ca<sup>2+</sup> entry mechanism in lymphocytes. Their role in cell migration and metastasis is demonstrated in solid cancers but it remains elusive in malignant hemopathies. Diffuse large B cell lymphoma (DLBCL) is characterized by the dissemination of neoplastic B cells throughout the organism which is under the control of chemokines such as Stromal Derived Factor 1 (SDF-1) and its receptor CXCR4. CXCR4 activation triggers a complex intracellular signaling including an increase in intracellular Ca<sup>2+</sup> concentration whose role is still unclear. Using pharmacological and genetic approaches, we revealed that STIM1 and Orai1 were responsible for Ca<sup>2+</sup> influx induced by SDF-1. Furthermore, we provide in vitro and in vivo evidence that they are necessary for basal or SDF-1-induced DLBCL cell migration which is independent of Ca<sup>2+</sup> entry. We identify that they act as effectors coupling RhoA and ROCK dependent signaling pathway to MLC2 phosphorylation and actin polymerization. Finally, we revealed an alteration of Orai1 and STIM1 expression in extra-nodal DLBCL. Thus, we discovered a novel Ca<sup>2+</sup>-independent but Orai1 and STIM1-dependent signaling pathway involved in basal and CXCR4 dependent cell migration, which could be relevant for DLBCL physiopathology. |
topic |
Orai1 STIM1 calcium migration lymphocyte lymphoma |
url |
https://www.mdpi.com/2072-6694/10/11/402 |
work_keys_str_mv |
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