Overexpression of transient receptor potential vanilloid 2 is associated with poor prognosis in patients with esophageal squamous cell carcinoma

Zhou, Kun; Zhang, Shui-Shen; Yan, Yan; Zhao, Song

doi:10.1007/s12032-014-0017-5

Cited by 45 publications

(31 citation statements)

References 24 publications

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“…Expression of TRP channels has been correlated with the aggressivity of multiple cancer forms, both in model systems [ 47 ] and in clinical investigations [ 48 , 49 ]. Similarly LL-37 has been linked to development and progression of various cancer forms.…”

Section: Discussionmentioning

confidence: 99%

Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells

et al. 2016

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Expression of the antimicrobial peptide hCAP18/LL-37 is associated to malignancy in various cancer forms, stimulating cell migration and metastasis. We report that LL-37 induces migration of three cancer cell lines by activating the TRPV2 calcium-permeable channel and recruiting it to pseudopodia through activation of the PI3K/AKT pathway. Ca2+ entry through TRPV2 cooperated with a K+ efflux through the BKCa channel. In a panel of human breast tumors, the expression of TRPV2 and LL-37 was found to be positively correlated. The D-enantiomer of LL-37 showed identical effects as the L-peptide, suggesting that no binding to a specific receptor was involved. LL-37 attached to caveolae and pseudopodia membranes and decreased membrane fluidity, suggesting that a modification of the physical properties of the lipid membrane bilayer was the underlying mechanism of its effects.

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Section: Discussionmentioning

confidence: 99%

Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells

et al. 2016

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“…Deregulation of TRPV2 expression has been reported in several solid cancers including prostate cancers, bladder cancers, hepatocellular carcinoma and esophageal squamous cell carcinoma (Santoni et al 2011). TRPV2 was always found expressed at higher levels in samples from patients with metastatic disease than in solid primary tumors and associated with poor prognosis, consistent with a role in metastasis formation (Caprodossi et al 2008;Monet et al 2010;Zhou et al 2014). TRPV2 characterization during prostate cancer progression best illustrates the tumorigenic potential of TRPV2.…”

Section: Trpvsmentioning

confidence: 90%

Constitutive calcium entry and cancer: updated views and insights

et al. 2017

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Tight control of basal cytosolic Ca concentration is essential for cell survival and to fine-tune Ca-dependent cell functions. A way to control this basal cytosolic Ca concentration is to regulate membrane Ca channels including store-operated Ca channels and secondary messenger-operated channels linked to G-protein-coupled or tyrosine kinase receptor activation. Orai, with or without its reticular STIM partner and Transient Receptor Potential (TRP) proteins, were considered to be the main Ca channels involved. It is well accepted that, in response to cell stimulation, opening of these Ca channels contributes to Ca entry and the transient increase in cytosolic Ca concentration involved in intracellular signaling. However, in various experimental conditions, Ca entry and/or Ca currents can be recorded at rest, without application of any experimental stimulation. This led to the proposition that some plasma membrane Ca channels are already open/activated in basal condition, contributing therefore to constitutive Ca entry. This article focuses on direct and indirect observations supporting constitutive activity of channels belonging to the Orai and TRP families and on the mechanisms underlying their basal/constitutive activities.

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“…We also assessed more than 200 ESCC patient samples, including fresh samples and para n slides, and found that TRPV2 was upregulated among > 87% of the fresh tumor samples and > 84% of the tumor slides compared with the non-tumor control samples. Previously, Zhou et al reported that overexpression of TRPV2 is associated with poor prognosis in patients with ESCC [55] and Atsushi proposed that TRPV2 is involved in the maintenance of CSCs (cancer stem cells) of ESCC [56]. Recently, Michihiro et al described that overexpression of TRPV2 in two ESCC cell lines (TE15 and KYSE170) and TRPV2 strong expression is associated with a worse prognosis in ESCC patients [57].…”

Section: Discussionmentioning

confidence: 99%

Thermal stress involved in TRPV2 promotes tumorigenesis through the pathway of PI3K/Akt/mTOR in esophageal squamous cell carcinoma

Huang¹,

Li²,

Tian³

et al. 2020

Preprint

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BackgroundEsophageal squamous cell carcinoma (ESCC) is a leading cause of cancer death worldwide. Although the exposure of esophageal mucosa to heat stimuli has long been recognized as an important risk for the initiation and development of ESCC, its underlying mechanisms remain uncharacterized. MethodsWestern blotting and immunofluorescence were used to detect the expression and localization of transient receptor potential vanilloid receptor 2 (TRPV2) in the ESCC cells. The cancerous behaviors of the ESCC cells were evaluated by a single-cell culturing assay, a wound healing assay, a 3D culturing assay and a tube formation assay respectively. In vivo tumorigenicity and metastasis of the ESCC cells were examined via xenograft nude mouse models. Western blotting and IHC were performed to determine the expression profiles of TRPV2 in the ESCC patient tissues. TRPV2 knocked-out ESCC cell line was established using CRISPR-Cas9 gene editing technique.ResultsHere, we found that the expression of TRPV2, one of the thermally sensitive TRP family members, was upregulated in both ESCC cells and clinical samples. We further showed that activation of TRPV2 by recurrent acute thermal stress (54°C, a temperature unexpectedly much lower than those in many dietary modalities) or O1821 (20 μM), a TRPV2 agonist, promoted cancerous behaviors in ESCC cells. The proangiogenic capacity of the heat-challenged ESCC cells was also found to be enhanced profoundly in the tube formation assay; both tumor formation and metastasis that originated from the cells were substantially promoted in nude mouse models upon the activation of TRPV2. These effects were inhibited significantly by tranilast (120 μM), a TRPV2 inhibitor, and abolished by TRPV2 knock-out using CRISPR-Cas9 gene editing. Conversely, overexpression of TRPV2 by transfection of TRPV2 DNA into NE2 cells, could switch the cells to tumorigenesis upon activation of TRPV2. Mechanistically, the driving role of TRPV2 in the progression of ESCC is mainly regulated by the PI3K/Akt/mTOR signaling pathway. Application of a pan-PI3K/mTOR inhibitor and/or a PTEN activator resulted in markedly reduced ESCC cell proliferation. ConclusionsOur study first proved that TRPV2 plays an important role in the tumorigenesis of ESCC upon thermal stress. We revealed that TRPV2-PI3K/Akt/mTOR is a novel and promising target for the prevention and treatment of ESCC.

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Overexpression of transient receptor potential vanilloid 2 is associated with poor prognosis in patients with esophageal squamous cell carcinoma

Cited by 45 publications

References 24 publications

Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells

Activation of TRPV2 and BKCa channels by the LL-37 enantiomers stimulates calcium entry and migration of cancer cells

Constitutive calcium entry and cancer: updated views and insights

Thermal stress involved in TRPV2 promotes tumorigenesis through the pathway of PI3K/Akt/mTOR in esophageal squamous cell carcinoma

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