TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway

Almasi, Shekoufeh; Sterea, Andra M.; Fernando, Wasundara; Clements, Derek R.; Marcato, Paola; Hoskin, David W.; Gujar, Shashi; Hiani, Yassine El

doi:10.1038/s41598-019-40330-1

Cited by 58 publications

(49 citation statements)

References 55 publications

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“…Both TRP channels and small GTPases have been implicated in increased tumor invasiveness through the induction of MMPs expression ( Betson and Braga, 2003 ; Yang and Kim, 2020 ). Indeed, TRPM2, TRPM7, TRPM8, TRPV2, and TRPC1 have shown to cause upregulation of MMP9 in a Ca 2+ -dependent manner in gastric, bladder, oral squamous, prostate and thyroid cancer cells respectively ( Monet et al, 2010 ; Okamoto et al, 2012 ; Asghar et al, 2015 ; Cao et al, 2016 ; Chen L. et al 2017 ; Chen Z. et al, 2017 ; Almasi et al, 2019 ). Additionally, TRPM2, TRPM7, and TRPC1 activity have been also correlated with MMP2 production in gastric, lung, pancreatic and thyroid cancer ( Asghar et al, 2015 ; Rybarczyk et al, 2017 ; Liu et al, 2018 ; Almasi et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, TRPM2, TRPM7, TRPM8, TRPV2, and TRPC1 have shown to cause upregulation of MMP9 in a Ca 2+ -dependent manner in gastric, bladder, oral squamous, prostate and thyroid cancer cells respectively ( Monet et al, 2010 ; Okamoto et al, 2012 ; Asghar et al, 2015 ; Cao et al, 2016 ; Chen L. et al 2017 ; Chen Z. et al, 2017 ; Almasi et al, 2019 ). Additionally, TRPM2, TRPM7, and TRPC1 activity have been also correlated with MMP2 production in gastric, lung, pancreatic and thyroid cancer ( Asghar et al, 2015 ; Rybarczyk et al, 2017 ; Liu et al, 2018 ; Almasi et al, 2019 ). On the other hand, Rho and Rac GTPases activation has been correlated with increased MMPs expression in different cancer cell types ( Zhuge and Xu, 2001 ; Abécassis et al, 2003 ; Santibáñez et al, 2010 ; Jacob et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“…TRPM2 offers another potential field of investigation on TRP-small GTPase relationship in cancer cells’ ability to invade surrounding tissues. In fact, it has been recently proven that TRPM2 causes an increase in MMP-9 production in gastric cancer ( Almasi et al, 2019 ). As in the case of TRPV4, the function of TRPM2 appears to be regulated by the Akt pathway, known to regulate the activity of several GTPases including Rac1 ( Ho et al, 2010 ), whose interaction with TRPM2 has been already well established in response to oxidative stress ( Gao et al, 2014 ) ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

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TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer

2020

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Transient Receptor Potential (TRP) cations channels, as key regulators of intracellular calcium homeostasis, play a central role in the essential hallmarks of cancer. Among the multiple pathways in which TRPs may be involved, here we focus our attention on the ones involving small guanosine triphosphatases (GTPases), summarizing the main processes associated with the metastatic cascade, such as migration, invasion and tumor vascularization. In the last decade, several studies have highlighted a bidirectional interplay between TRPs and small GTPases in cancer progression: TRP channels may affect small GTPases activity via both Ca 2+ -dependent or Ca 2+ -independent pathways, and, conversely, some small GTPases may affect TRP channels activity through the regulation of their intracellular trafficking to the plasma membrane or acting directly on channel gating. In particular, we will describe the interplay between TRPC1, TRPC5, TRPC6, TRPM4, TRPM7 or TRPV4, and Rho-like GTPases in regulating cell migration, the cooperation of TRPM2 and TRPV2 with Rho GTPases in increasing cell invasiveness and finally, the crosstalk between TRPC1, TRPC6, TRPM8, TRPV4 and both Rho- and Ras-like GTPases in inducing aberrant tumor vascularization.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer

2020

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“…The opening of TRP channels can promote Ca 2+ entry which activates downstream signaling pathways, such as Ca 2+ /calmodulin kinase II (CaMKII), mitogen-activated protein kinase (MAPK), AMPK and so on to control cell proliferation, apoptosis and migration [41,42]. Over the past two decades, several research groups including ours have identi ed six TRP channels (TRPC6, TRPM2, 5, 7, TRPV4, 6) that play an important role in GC development [6][7][8][43][44][45][46]. However, all these six TRP channels have been suggested as oncogene and tumor promoter in GC.…”

Section: Discussionmentioning

confidence: 99%

A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development

Gao

Feng

Chen

et al. 2020

Preprint

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Background: Although the aberrant expression and function of most Ca2+-permeable channels are known to promote gastrointestinal tumors, the association of transient receptor potential vanilloid receptor 1(TRPV1) channels and gastric cancer (GC) has not been explored so far. We sought to determine their role in the development of GC and to elucidate the underlying molecular mechanisms. Methods: The expression of TRPV1 in GC cells and tissues was detected by qPCR, immunohistochemistry, western blot analysis and immunofluorescence. CCK8 and flow cytometry were used to detect the proliferation and cell cycle, while transwell assay was used to detect migration and invasion. The role of TRPV1 in GC development in vivo was tested using tumor xenograft and peritoneal dissemination assays in nude mice. Results: The decreased expression of TRPV1 protein in primary human GC tissues was closely correlated with poor prognosis of GC patients. TRPV1 protein was predominately expressed on the plasma membrane of several GC cell lines. TRPV1 overexpression attenuated proliferation, migration and invasion of GC cells in vitro, but TRPV1 knockdown increased them. Moreover, TRPV1 significantly reduced gastric tumor sizes, numbers and peritoneal dissemination in vivo. Mechanistically, TRPV1 overexpression increased [Ca2+]i, activated CaMKKβ and AMPK phosphorylation, and decreased expression of cyclin D1 and MMP2, but TRPV1 knockdown caused the opposite effects.Conclusions: TRPV1 uniquely suppresses GC through a novel Ca2+/CaMKKβ/AMPK pathway and its downregulation is correlated with poor survival in human GC. TRPV1 upregulation and its downstream signaling may be a promising strategy for GC prevention and therapy.

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“…TRPM4 also regulates mechanotransduction in cell migration via promotion of focal adhesion disassembly, activation of FAK activation and Rac1, and actin cytoskeleton reorganization (76). Recently, it has been shown that TRPM2 regulates migration and invasion of gastric cancer cells in vitro, and also tumorigenesis and expression of N-cadherin, snail, slug, integrins, and MMPs that are representative epithelial-mesenchymal transition (EMT) markers in vivo (77).…”

Section: Trp Channels In Cancer Metastasismentioning

confidence: 99%

Emerging role of transient receptor potential (TRP) channels in cancer progression

Yang

Kim

2020

BMB Rep.

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Transient receptor potential (TRP) channels comprise a diverse family of ion channels, the majority of which are calcium permeable and show sophisticated regulatory patterns in response to various environmental cues. Early studies led to the recognition of TRP channels as environmental and chemical sensors. Later studies revealed that TRP channels mediated the regulation of intracellular calcium. Mutations in TRP channel genes result in abnormal regulation of TRP channel function or expression, and interfere with normal spatial and temporal patterns of intracellular local Ca 2+ distribution. The resulting dysregulation of multiple downstream effectors, depending on Ca 2+ homeostasis, is associated with hallmarks of cancer pathophysiology, including enhanced proliferation, survival and invasion of cancer cells. These findings indicate that TRP channels affect multiple events that control cellular fate and play a key role in cancer progression. This review discusses the accumulating evidence supporting the role of TRP channels in tumorigenesis, with emphasis on prostate cancer. [BMB Reports 2020; 53(3): 125-132]

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TRPM2 ion channel promotes gastric cancer migration, invasion and tumor growth through the AKT signaling pathway

Cited by 58 publications

References 55 publications

TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer

TRP Channels and Small GTPases Interplay in the Main Hallmarks of Metastatic Cancer

A Unique Role Of TRPV1 Ion Channels In The Suppression Of Gastric Cancer Development

Emerging role of transient receptor potential (TRP) channels in cancer progression

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