Effect of P2X7 receptor on tumorigenesis and its pharmacological properties

Zhang, Wenjun; Hu, Cegui; Zhu, Zhengming; Luo, Haiwei

doi:10.1016/j.biopha.2020.109844

Cited by 40 publications

(26 citation statements)

References 153 publications

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“…Thus, it is possible that the sustained Ca 2+ signal reported in our studies is due to Ca 2+ uptake through ATP-activated P2X7R, and that there is an undetectable first, sharp peak of Ca 2+ released through the IP 3 R present in the endoplasmic reticulum. In addition, many studies have shown that the P2X7R and the tumor microenvironment play an important role in regulating the growth, apoptosis, migration and invasion of tumor cells (reviewed in Zhang et al, 2020). Involvement of the P2X7R has been described in tamoxifen-resistant MCF-7 breast cancer cells, where activity of this receptor seems to be restricted to cell migration and metastasis, rather than cell proliferation (Park et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca2+/P2X7 Receptor Signaling Axis

Brenet

Martı́nez

Pérez-Núñez

et al. 2021

Front. Cell Dev. Biol.

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Cancer cell adhesion to the vascular endothelium is an important step in tumor metastasis. Thy-1 (CD90), a cell adhesion molecule expressed in activated endothelial cells, has been implicated in melanoma metastasis by binding to integrins present in cancer cells. However, the signaling pathway(s) triggered by this Thy-1-Integrin interaction in cancer cells remains to be defined. Our previously reported data indicate that Ca2+-dependent hemichannel opening, as well as the P2X7 receptor, are key players in Thy-1-αVβ3 Integrin-induced migration of reactive astrocytes. Thus, we investigated whether this signaling pathway is activated in MDA-MB-231 breast cancer cells and in B16F10 melanoma cells when stimulated with Thy-1. In both cancer cell types, Thy-1 induced a rapid increase in intracellular Ca2+, ATP release, as well as cell migration and invasion. Connexin and Pannexin inhibitors decreased cell migration, implicating a requirement for hemichannel opening in Thy-1-induced cell migration. In addition, cell migration and invasion were precluded when the P2X7 receptor was pharmacologically blocked. Moreover, the ability of breast cancer and melanoma cells to transmigrate through an activated endothelial monolayer was significantly decreased when the β3 Integrin was silenced in these cancer cells. Importantly, melanoma cells with silenced β3 Integrin were unable to metastasize to the lung in a preclinical mouse model. Thus, our results suggest that the Ca2+/hemichannel/ATP/P2X7 receptor-signaling axis triggered by the Thy-1-αVβ3 Integrin interaction is important for cancer cell migration, invasion and transvasation. These findings open up the possibility of therapeutically targeting the Thy-1-Integrin signaling pathway to prevent metastasis.

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Section: Discussionmentioning

confidence: 99%

Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca2+/P2X7 Receptor Signaling Axis

Brenet

Martı́nez

Pérez-Núñez

et al. 2021

Front. Cell Dev. Biol.

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“…In the early stage, the function of P2 × 7 receptor was recognized mainly related to immune and inflammatory response. With the exploration of the function of P2 × 7 receptor, it was found that P2 × 7 receptor is closely related to the development of tumors (Zhang et al, 2020). Indeed, P2 × 7 receptor is expressed in a variety of tumor cells, such as lung cancer, prostate cancer, liver cancer, non-small cell cancer, and is closely related to the growth, proliferation, apoptosis, migration and invasion of tumors (Gilbert et al, 2019;Park et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…P2 × 7 receptor widely distributed in human tissue structure (Kan et al, 2019). P2 × 7 receptor is activated by ATP, which can open a pore for cations on the cell membrane (sodium and calcium ions influx, potassium ions outflow), allow molecules less than 900 Da to pass freely, affect the stability of the cell membrane skeleton and cell membrane fluidity, trigger intracellular molecular imbalance (Zhang et al, 2020). Certainly, P2 × 7 receptor plays an important regulatory role in tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling

Zhang

Luo

et al. 2020

Front. Cell Dev. Biol.

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The pathological mechanism of colon cancer is very complicated. Therefore, exploring the molecular basis of the pathogenesis of colon cancer and finding a new therapeutic target has become an urgent problem to be solved in the treatment of colon cancer. ATP plays an important role in regulating the progression of tumor cells. P2 × 7 belongs to ATP ion channel receptor, which is involved in the progression of tumors. In this study, we explored the effect and molecular mechanism of ATP-mediated P2 × 7 receptor on the migration and metastasis of colon cancer cells. The results showed that ATP and BzATP significantly increased the inward current and intracellular calcium concentration of LOVO and SW480 cells, while the use of antagonists (A438079 and AZD9056) could reverse the above phenomenon. We found that ATP promoted the migration and invasion of LOVO and SW480 cells and is dose-dependent on ATP concentration (100–300 μM). Similarly, BzATP (10, 50, and 100 μM) also significantly promoted the migration and invasion of colon cancer cells in a concentration-dependent manner. While P2 × 7 receptor antagonists [A438079 (10 μM), AZD9056 (10 μM)] or P2 × 7 siRNA could significantly inhibit ATP-induced colon cancer cell migration and invasion. Moreover, in vivo experiments showed that ATP-induced activation of P2 × 7 receptor promoted the growth of tumors. Furthermore, P2 × 7 receptor activation down-regulated E-cadherin protein expression and up-regulated MMP-2 mRNA and concentration levels. Knocking down the expression of P2 × 7 receptor could significantly inhibit the increase in the expression of N-cadherin, Vimentin, Zeb1, and Snail induced by ATP. In addition, ATP time-dependently induced the activation of STAT3 via the P2 × 7 receptor, and the STAT3 pathway was required for the ATP-mediated invasion and migration. Our conclusion is that ATP-induced P2 × 7 receptor activation promotes the migration and invasion of colon cancer cells, possibly via the activation of STAT3 pathway. Therefore, the P2 × 7 receptor may be a potential target for the treatment of colon cancer.

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“…Salaro et al showed that NLRP3 was significantly downmodulated in CLL lymphocytes compared to those of healthy donors, whereas the P2X7 receptor (P2X7R) was overexpressed [80]. P2X7R is mainly known as an activator of the NLRP3 inflammasome [30,86], but it also prevents apoptosis and promotes cell proliferation [87]. The expression of P2X7R is controlled by NLRP3, such that the downmodulation of NLRP3 drives P2X7R expression and simultaneously contributes to tumor growth, whereas NLRP3 overexpression inhibits cell proliferation and induces cell death.…”

Section: Chronic Lymphocytic Leukemia (Cll)mentioning

confidence: 99%

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

Urwanisch

Luciano

Horejs‐Hoeck

2021

IJMS

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Chronic inflammation contributes to the development and progression of various tumors. Especially where the inflammation is mediated by cells of the innate immune system, the NLRP3 inflammasome plays an important role, as it senses and responds to a variety of exogenous and endogenous pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). The NLRP3 inflammasome is responsible for the maturation and secretion of the proinflammatory cytokines interleukin-1β (IL-1β) and IL-18 and for the induction of a type of inflammatory cell death known as pyroptosis. Overactivation of the NLRP3 inflammasome can be a driver of various diseases. Since leukemia is known to be an inflammation-driven cancer and IL-1β is produced in elevated levels by leukemic cells, research on NLRP3 in the context of leukemia has increased in recent years. In this review, we summarize the current knowledge on leukemia-promoting inflammation and, in particular, the role of the NLRP3 inflammasome in different types of leukemia. Furthermore, we examine a connection between NLRP3, autophagy and leukemia.

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Effect of P2X7 receptor on tumorigenesis and its pharmacological properties

Cited by 40 publications

References 153 publications

Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca2+/P2X7 Receptor Signaling Axis

Thy-1 (CD90)-Induced Metastatic Cancer Cell Migration and Invasion Are β3 Integrin-Dependent and Involve a Ca2+/P2X7 Receptor Signaling Axis

Activation of P2×7 Receptor Promotes the Invasion and Migration of Colon Cancer Cells via the STAT3 Signaling

The NLRP3 Inflammasome and Its Role in the Pathogenicity of Leukemia

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