When S1P meets ATP

Burow, Philipp; Markwardt, Fritz

doi:10.4161/19336950.2014.959408

Cited by 5 publications

(4 citation statements)

References 8 publications

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“…Sphingosine kinase 1 (SPHK1), the most important synthetase for sphingosine-1-phosphate (S1P), is involved in tumour progression in various cancer cells [[18], [19], [20], [21]]. Studies have shown that VRAC can be activated by S1P and that high expression of SPHK1/S1P promotes the proliferation of HCC [21,22]. Because SWELL1 is an essential component of VRAC, we speculated about the possible relationship between SPHK1 and SWELL1 in the proliferation of HCC.…”

Section: Resultsmentioning

confidence: 99%

“…For further confirmation, MMP and intracellular ATP measurements were analysed, and the results were in agreement with ROS measurements. Moreover, S1P has been found to induce ATP secretion by activating the VRAC [22], and ATP is a known growth factor for tumour cells [39,40]. Thus, to some degree, the enhancement effect of SWELL1 on ATP content also verified the proliferative effect of the SPHK1-SWELL1-PKCa pathway on HCC.…”

Section: Discussionmentioning

confidence: 99%

“…As mentioned above, SPHK1 can enhance HCC cell proliferation [21]. Moreover, S1P has been shown to affect the activity of VRAC [22]. As the most important synthetase of S1P, SPHK1 might be relevant to SWELL1-mediated proliferation in HCC.…”

Section: Discussionmentioning

confidence: 99%

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SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo

Ding

et al. 2019

EBioMedicine

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Background: SWELL1 was recently demonstrated to be an indispensable part of the volume-regulated anion channel (VRAC). VRAC is reported to participate in cell proliferation, survival, and migration. However, the correlation between SWELL1 and hepatocellular carcinoma (HCC) remains poorly-understood. In this study, we tried to explore the role of SWELL1 in HCC. Methods: Immunohistochemistry and quantitative real-time-PCR (qRT-PCR) was used to measure SWELL1 expression in HCC samples obtained from patients with HCC. The effects of SWELL1 on HCC cell proliferation, apoptosis, and metastasis were analysed by corresponding cytological experiments including Cell Counting Kit-8 (CCK8), colony-forming, 5-ethynyl-2-deoxyuridine (EdU), cell cycle analysis, TUNEL, Annexin V and PI staining, wound healing, transwell, and so on. BALB/c nude mice were used for the in vivo assays. qRT-PCR and western blotting was performed for molecular mechanisms. Findings: SWELL1 was highly expressed in HCC tissues, and related to the poor prognosis. In vitro, the over-expression of SWELL1 significantly induced cell proliferation and migration, and inhibited apoptosis, whereas suppressing SWELL1 had the opposite effects. Moreover, knockdown of SWELL1 suppressed the growth and metastasis of HCC in vivo. Further experiments revealed that SWELL1 induced cell growth by activating the cyclinD1/CDK2 pathway via the connection with PKCa at the signalling level, and regulated cell migration through the JNK pathway in HCC. Interpretation: SWELL1 acts as a promoter in the growth and metastasis of HCC cells and may be a potential intervention target for HCC.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo

Ding

et al. 2019

EBioMedicine

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“…S1P induced ATP release via VRAC formed an autocrine link between inflammatory sphingolipid and purinergic signaling in macrophages (Burow P et al, 2015) and microglia (Zahiri D et al, 2021). S1P is an inflammatory mediator and is produced by sphingosine kinase, which is activated by several inflammatory signaling molecules, including bacterial b b lipopolysaccharide (LPS), PDGF, TNFα, thrombin, IgE-bound antigen and ATP (Burow P et al, 2015; Burow P and Markwardt F, 2014). S1P is rich in the cancer microenvironment (Nagahashi M et al 2012) and plays important roles in cancer progression via diverse pathways of its G-protein coupled receptors, which implicates S1P pathway as a therapeutic target (Pyne NJ and Pyne S, 2010; Ogretmen B, 2018; Nagahashi M et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Hypo-osmotic Stress Induces ATP Release via Volume-regulated Anion Channels in Undifferentiated Mammary Cells

Furuya

Takahashi

Hirata

et al. 2021

Preprint

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The high interstitial ATP concentration in the cancer microenvironment is a major source of adenosine, which acts as a strong immune suppressor. However, the source of ATP release has not been elucidated. We measured the ATP release during hypotonic stress using a real-time ATP luminescence imaging system in primary cultured mammary cells and in breast cell lines. In primary cultured cells, ATP was intermittently released with transient-sharp peaks, while in breast cell lines ATP was released with a slowly rising diffuse pattern. The diffuse ATP release pattern was changed to a transient-sharp pattern by cholera toxin treatment and the reverse change was induced by transforming growth factor (TGF) β treatment. DCPIB, an inhibitor of volume-regulated anion channels (VRACs), only suppressed the diffuse pattern. The inflammatory mediator sphingosine-1-phosphate (S1P) induced a diffuse ATP release pattern isovolumetrically. The knockdown of A isoform of leucine-rich repeat-containing protein 8 (LRRC8A), the essential molecular entity of VRACs, using shRNA suppressed the diffuse pattern. These results suggest that abundantly expressed VRACs are a conduit of ATP release in undifferentiated cells, including cancer cells.

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Ion channels in regulated cell death

Kunzelmann

2016

Cell. Mol. Life Sci.

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Activation of ion channels and pores are essential steps during regulated cell death. Channels and pores participate in execution of apoptosis, necroptosis and other forms of caspase-independent cell death. Within the program of regulated cell death, these channels are strategically located. Ion channels can shrink cells and drive them towards apoptosis, resulting in silent, i.e. immunologically unrecognized cell death. Alternatively, activation of channels can induce cell swelling, disintegration of the cell membrane, and highly immunogenic necrotic cell death. The underlying cell death pathways are not strictly separated as identical stimuli may induce cell shrinkage and apoptosis when applied at low strength, but may also cause cell swelling at pronounced stimulation, resulting in regulated necrosis. Nevertheless, the precise role of ion channels during regulated cell death is far from being understood, as identical channels may support regulated death in some cell types, but may cause cell proliferation, cancer development, and metastasis in others. Along this line, the phospholipid scramblase and Cl(-)/nonselective channel anoctamin 6 (ANO6) shows interesting features, as it participates in apoptotic cell death during lower levels of activation, thereby inducing cell shrinkage. At strong activation, e.g. by stimulation of purinergic P2Y7 receptors, it participates in pore formation, causes massive membrane blebbing, cell swelling, and membrane disintegration. The LRRC8 proteins deserve much attention as they were found to have a major role in volume regulation, apoptotic cell shrinkage and resistance towards anticancer drugs.

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When S1P meets ATP

Abstract: Burow P, Klapperst€ uck M, Markwardt F. Activation of ATP secretion via volume-regulated anion channels by sphingosine-1-phosphate in RAW macrophages.

Cited by 5 publications

References 8 publications

SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo

SWELL1 promotes cell growth and metastasis of hepatocellular carcinoma in vitro and in vivo

Hypo-osmotic Stress Induces ATP Release via Volume-regulated Anion Channels in Undifferentiated Mammary Cells

Ion channels in regulated cell death

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