Epithelial–mesenchymal transition, IP3 receptors and ER–PM junctions: translocation of Ca2+ signalling complexes and regulation of migration

Okeke, Emmanuel Sunday; Parker, Tony J.; Dingsdale, Hayley; Concannon, Matthew J.; Awais, Muhammad; Voronina, Svetlana; Molgó, Jordi; Begg, Malcolm; Metcalf, Daniel; Knight, Alex E.; Sutton, Robert; Haynes, Lee P.; Tepikin, Alexei V.

doi:10.1042/bj20150364

Cited by 21 publications

(24 citation statements)

References 55 publications

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“…13 Interestingly, intracellular Ca 2þ fluctuations are involved in tumor cell dissemination influencing migration and vesicle trafficking. 16,33 Along these lines, monoallelic loss of Atg5 influenced FBSmediated migration/invasion, FBS-induced Ca 2þ responses as well as expression of Ca 2þ handling proteins. In support, Atg5 expression was recently linked to heightened tumor cell metastasis via disrupting the V1Vo ATPase, which is closely connected to cytosolic Ca 2þ , indicating a pathway through which a autophagy-related gene can promote metastasis in an autophagy-independent manner.…”

Section: Discussionmentioning

confidence: 99%

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

Görgülü

Diakopoulos

et al. 2019

Gastroenterology

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Section: Discussionmentioning

confidence: 99%

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

Görgülü

Diakopoulos

et al. 2019

Gastroenterology

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“…[ 20 ] elegantly demonstrate that caffeine, at concentration that inhibits IP 3 R3 preferentially to the two other IP 3 R subtypes, is able to inhibit migration and invasion of glioblastoma cells in vitro . Moreover, IP 3 Rs inhibition markedly reduces the migration of pancreatic adenocarcinoma cells by modulating the Ca 2+ signaling complexes [ 42 ]. We establish a link between an oscillating IP 3 - dependent Ca 2+ signal and the migration capacity of breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca2+ signal

Mound¹,

Vautrin-Glabik²,

Foulon³

et al. 2017

Oncotarget

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Breast cancer remains a research priority due to its invasive phenotype. Although the role of ion channels in cancer is now well established, the role of inositol (1,4,5)-trisphosphate (IP3) receptors (IP3Rs) remains enigmatic. If the three IP3Rs subtypes expression have been identified in various cancers, little is known about their physiological role. Here, we investigated the involvement of IP3R type 3 (IP3R3) in the migration processes of three human breast cancer cell lines showing different migration velocities: the low-migrating MCF-7 and the highly migrating and invasive MDA-MB-231 and MDA-MB-435S cell lines. We show that a higher IP3R3 expression level, but not IP3R1 nor IP3R2, is correlated to a stronger cell line migration capacity and a sustained calcium signal. Interestingly, silencing of IP3R3 highlights an oscillating calcium signaling profile and leads to a significant decrease of cell migration capacities of the three breast cancer cell lines. Conversely, stable overexpression of IP3R3 in MCF-7 cells significantly increases their migration capacities. This effect is completely reversed by IP3R3 silencing. In conclusion, we demonstrate that IP3R3 expression level increases the migration capacity of human breast cancer cells by changing the calcium signature.

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“…The EMT process is stimulated upon loss of cell-cell contact and occurs in migrating cancer cells (Gheldof and Berx, 2013). It has been shown in disconnected individual PANC-1 cells that ER/Plasma membrane junctions containing STIM1, together with the IP 3 Rs, redistribute to the leading edge of focal adhesions (Okeke et al, 2016). An inhibition of IP 3 Rs and SOC entry reduced the migrating capacity of PANC-1 cells.…”

Section: Orai and Stimmentioning

confidence: 99%

Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma

et al. 2020

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Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancerrelated 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.

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Epithelial–mesenchymal transition, IP3 receptors and ER–PM junctions: translocation of Ca2+ signalling complexes and regulation of migration

Cited by 21 publications

References 55 publications

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

Levels of the Autophagy-Related 5 Protein Affect Progression and Metastasis of Pancreatic Tumors in Mice

Downregulation of type 3 inositol (1,4,5)-trisphosphate receptor decreases breast cancer cell migration through an oscillatory Ca2+ signal

Ion Channel Signature in Healthy Pancreas and Pancreatic Ductal Adenocarcinoma

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