Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives

Roger, Sébastien; Jelassi, Bilel; Couillin, Isabelle; Pelegrı́n, Pablo; Besson, Pierre; Jiang, Lin‐Hua

doi:10.1016/j.bbamem.2014.10.029

Cited by 83 publications

(95 citation statements)

References 242 publications

(369 reference statements)

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“…P2X7R, an ATP-gated cation permeable (Na and an efflux of K 1 . This leads to intracellular signaling pathways that are associated with numerous physiologic processes correlated to inflammatory cascade induction and cell survival and proliferation (Bianco et al, 2009;Roger et al, 2015). In contrast, upon repeated and/or prolonged ATP stimulation, P2X7R induces the opening of nonspecific larger pores that allow permeation of molecules up to 900 Da generally associated with cell death, such as ethidium bromide and Yo-Pro-1 (Bianco et al, 2009;Volonte et al, 2012;Roger et al, 2015).…”

Section: The Ionotropic Atp-gated P2x7 Receptormentioning

confidence: 99%

“…One hypothesis suggests that P2X7R is an antitumor protein that induces cancer cell death, and the other proposes that P2X7R is an aggressive protein that promotes cancer cell survival and growth or invasiveness (Roger and Pelegrin, 2011). P2X7R is expressed at both the mRNA and protein level in human and in mouse glioma cells (Roger et al, 2015).…”

Section: The Ionotropic Atp-gated P2x7 Receptormentioning

confidence: 99%

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Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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Malignant brain tumors are highly lethal and aggressive. Despite recent advances in the current therapies, which include the combination of surgery and radio/chemotherapy, the average survival rate remains poor. Altered regulation of ion channels is part of the neoplastic transformation, which suggests that ion channels are involved in cancer. Distinct classes of calciumpermeable channels are abnormally expressed in cancer and are likely involved in the alterations underlying malignant growth. Specifically, cytosolic Ca 21 activity plays an important role in the regulation of cell proliferation, and Ca 21 signaling is altered in proliferating tumor cells. A series of previous studies emphasized the importance of the T-type low-voltage-gated calcium channels (VGCC) in different cancer types, including gliomas, and remarkably, pharmacologic inhibition of T-type VGCC caused antiproliferative effects and triggered apoptosis of human glioma cells. Other calcium permeable channels, such as transient receptor potential (TRP) channels, contribute to changes in Ca 21 by modulating the driving force for Ca 21 entry, and some TRP channels are required for proliferation and migration in gliomas. Furthermore, recent evidence shows that TRP channels contribute to the progression and survival of the glioblastoma patients. Likewise, the purinergic P2X7 receptor acts as a direct conduit for Ca 21 -influx and an indirect activator of voltage-gated Ca 21 -channel. Evidence also shows that P2X7 receptor activation is linked to elevated expression of inflammation promoting factors, tumor cell migration, an increase in intracellular mobilization of Ca 21 , and membrane depolarization in gliomas. Therefore, this review summarizes the recent findings on calcium channels and associated receptors as potential targets to treat malignant gliomas.

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Section: The Ionotropic Atp-gated P2x7 Receptormentioning

confidence: 99%

Section: The Ionotropic Atp-gated P2x7 Receptormentioning

confidence: 99%

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Morrone¹,

Gehring²,

Nicoletti³

2016

Mol Pharmacol

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“…In prostate tumors, overexpressed mouse orthologue cathelicidin-related AMP (CRAMP) initially chemo-attracts immature myeloid progenitors (IMPs) to the tumor microenvironment (TME) and mediates differentiation and polarization of early myeloid progenitors into protumorigenic type 2 (M2) macrophages to help drive prostate cancer progression [62]. The stimulation of P2X 7 can promote migration of PC9 lung cells and T47D breast cancer cells [30], suggesting involvement of a similar P2X 7 -based mechanism in other solid tumors [63]. P2X 7 can trigger massive release of vascular endothelial growth factor (VEGF) from immune cells as well as tumor cells [31].…”

Section: Prostate Cancermentioning

confidence: 99%

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

Chen

Zou

et al. 2018

Cell Physiol Biochem

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LL-37, the C-terminal peptide of human cathelicidin antimicrobial peptide (CAMP, hCAP18), reportedly increases resistance to microbial invasion and exerts important physiological functions in chemotaxis, promotion of wound closure, and angiogenesis. Accumulating evidence indicates that LL-37 also plays a significant role in human cancer. LL-37 induces tumorigenic effects in cancers of the ovary, lung, breast, prostate, pancreas, as well as in malignant melanoma and skin squamous cell carcinoma. In contrast, LL-37 displays an anti-cancer effect in colon cancer, gastric cancer, hematologic malignancy and oral squamous cell carcinoma. Mechanistically, LL-37-induced activation of membrane receptors and subsequent signaling pathways lead to alteration of cellular functions. Different membrane receptors on various cancer cells appear to be responsible for the tissue-specific effects of LL-37. Meanwhile, the findings that vitamin D-dependent induction of cathelicidin in human macrophages activates the anti-cancer activity of tumor-associated macrophages (TAMs) and enhances antibody-dependent cellular cytotoxicity (ADCC) support critical roles of vitamin D-dependent induction of cathelicidin in cancer progression. This review describes novel advances involving the roles and mechanisms of human cathelicidin LL-37 in cancer.

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“…Ultraviolet radiation is the major causative factor of these skin cancers [110] . P2X7 is emerging as an important receptor in many forms of cancers, with various and contradictory roles attributed to this receptor in tumour biology [111] . These include but are not limited to tumour cell proliferation [112] , death [113] , and invasiveness [114] , as well as anti-tumour immunity [115] and cancer pain [116] .…”

Section: Skin Cancermentioning

confidence: 99%

P2X7 receptor in skin biology and diseases

Geraghty¹,

Watson²,

Adhikary³

et al. 2016

WJD

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The P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer. AbstractThe P2X7 receptor is a trimeric ligand-gated cation channel present on immune and other cells. Activation of this receptor by its natural ligand extracellular adenosine triphosphate results in a variety of downstream responses, including the release of pro-inflammatory mediators and cell death. In normal skin, P2X7 is present on keratinocytes, Langerhans cells and fibroblasts, while the presence of this receptor on other cutaneous cells is mainly inferred from studies of equivalent cell types present in other tissues. Mast cells in normal skin however express negligible amounts of P2X7, which can be upregulated in cutaneous disease. This review discusses the potential significance of P2X7 in skin biology, and the role of this receptor in inflammatory skin disorders such as irritant and chronic dermatitis, psoriasis, graft-versus-host disease, as well is in wound healing, transplantation and skin cancer. Core tip: The P2X7 receptor is present on immune, stromal and epithelial cells. Activation of this receptor by its natural ligand, extracellular adenosine triphosphate, causes a variety of downstream effects including release of inflammatory mediators and growth factors, as well as cell death. P2X7 has various functions on skin cells, and studies of mouse models of disease and of human cells and tissues highlight emerging roles for this receptor in common skin disorders.

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Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives

Cited by 83 publications

References 242 publications

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Calcium Channels and Associated Receptors in Malignant Brain Tumor Therapy

Roles and Mechanisms of Human Cathelicidin LL-37 in Cancer

P2X7 receptor in skin biology and diseases

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