High expression of P2X7R is an independent postoperative indicator of poor prognosis in colorectal cancer

Qian, Fei; Xiao, Jianjia; Hu, Baoying; Sun, Naizhi; Zhu, Jianwei

doi:10.1016/j.humpath.2017.03.019

Cited by 43 publications

(36 citation statements)

References 16 publications

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“…Western blot analysis was performed as previously described . Briefly, CRC tissues and cell lines were homogenized using RIPA lysis buffer (Beyotime, Shanghai) supplemented with protease and phosphatase inhibitor cocktails (Roche Diagnostics, Basel, Switzerland).…”

Section: Meterials and Methodsmentioning

confidence: 99%

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HMGB1‐RAGE signaling facilitates Ras‐dependent Yap1 expression to drive colorectal cancer stemness and development

Qian

Xiao

Gai

et al. 2018

Molecular Carcinogenesis

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HMGB1-RAGE signaling plays an integral role in inflammation-driven carcinogenesis.In the present study, we showed that RAGE has direct association with K-Ras following HMGB1 exposure in colorectal cancer (CRC) cells. Immunofluorescence analysis revealed a significant co-localization between RAGE and K-Ras in HMGB1-exposed CRC cells. Moreover, we uncovered that HMGB1-mediated RAGE activation led to Yap1 accumulation in a Ras-dependent mechanism in CRC cells. HMGB1 activated the expression of Yap1 downstream stemness marker proteins CD44 and Sox2 in RAGEand Ras-dependent manners. Furthermore, HMGB1 exposure led to the proliferation of CRC cells and the expansion of CRC stem cells. RAGE, Yap1 and CD44 were overexpressed in CRC specimens. Linear regression analysis revealed that the expression of RAGE was positively correlated with Yap1 in clinical CRC specimens. Both of RAGE and Yap1 expression were correlated with advanced histological grades, lymph node metastasis and TNM stages. Finally, we revealed that both of RAGE and Yap1 expression could predicted unfavorable prognosis in CRC patients. These findings implicated that HMGB1-RAGE signaling may promote Yap1 activation and CRC progression, shedding new light on the mechanisms underlying inflammationdriven CRC development. K E Y W O R D S colorectal cancer, HMGB1, K-Ras, RAGE, stemness, Yap1

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Section: Meterials and Methodsmentioning

confidence: 99%

“…Some major clinicopathologic data of the patients can be found in Table . Immunohistochemistry and immunohistochemistrical evaluation were conducted as previously reported . The study has been approved by the Ethics Committee of Affiliated Hospital of Nantong University and written consent was obtained from every patient.…”

Section: Meterials and Methodsmentioning

confidence: 99%

HMGB1‐RAGE signaling facilitates Ras‐dependent Yap1 expression to drive colorectal cancer stemness and development

Qian

Xiao

Gai

et al. 2018

Molecular Carcinogenesis

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“…Via activation of the NLRP3 inflammasome pathway and ROS generation, purinergic receptors are involved in the pathogenesis of many of these diseases-including liver fibrosis [48], diabetes [49], and neuroinflammation [50]. The overexpression of purinergic receptors (especially P2X7R) is thought to be involved in tumorigenesis [36,[51][52][53][54][55]. Studies of ethanol's immunomodulatory effect on macrophages have recently highlighted the involvement of the NLRP3 inflammasome.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, P2Y6R was linked to the development of pulmonary fibrosis [29], and P2X7R is thought to be involved in Parkinson's disease, pulmonary hypertension, gout, allergy, pulmonary fibrosis, and alcoholic and nonalcoholic steatohepatitis [30][31][32][33][34][35]. Furthermore, high P2X7R expression levels may indicate a poor prognosis for patients with colorectal cancer [36]. In the present paper, we used BzATP, a potent agonist of P2X7R, in order to activate NLRP3 inflammasome through purinergic receptor pathway.…”

Section: Introductionmentioning

confidence: 99%

Ethanol upregulates the P2X7 purinergic receptor in human macrophages

Daré

Victoni

Bodin

et al. 2018

Fundamemntal Clinical Pharma

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Alcohol consumption is considered to be the third leading cause of death in the United States. In addition to its direct toxicity, ethanol has two contrasting effects on the immune system: the nucleotide oligomerization domain‐like receptor pyrin domain‐containing‐3 (NLRP3) inflammasome is inhibited by acute ethanol exposure but activated by chronic ethanol exposure. Purinergic receptors (especially the P2X7 receptor) are able to activate the NLRP3 inflammasome and are involved in many ethanol‐related diseases (such as gout, pulmonary fibrosis, alcoholic steatohepatitis, and certain cancers). We hypothesized that ethanol regulates purinergic receptors and thus modulates the NLRP3 inflammasome's activity. In experiments with monocyte‐derived macrophages, we found that interleukin (IL)‐1β secretion was inhibited after 7 h of exposure (but not 48 h of exposure) to ethanol. The disappearance of ethanol's inhibitory effect on IL‐1β secretion after 48 h was not mediated by the upregulated production of IL‐1β, IL‐1α, IL‐6 or the inflammasome components NLRP3, apoptosis‐associated speck‐like protein containing a caspase recruitment domain, and caspase 1. P2X7R expression was upregulated by ethanol, whereas expression of the P2X4 and P2X1 receptors was not. Taken as a whole, our results suggest that ethanol induces NLRP3 inflammasome activation by upregulating the P2X7 receptor. This observation might have revealed a new mechanism for inflammation in ethanol‐related diseases.

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“…P2X7R localized to the cytoplasmic membrane is considered to be an important mediator for tumor invasion and metastasis as well as its role in inflammation and aerobic glycolysis [12]. In a few recent studies, it is claimed that P2X7R expression in tumor cells associated with aggressive clinical features and poor prognosis in patients with colorectal cancer (CRC) [14,15]. In another study, it was reported that P2X7R regulates the cell survival and cell migration in ductal pancreatic adenocarcinoma cells, and P2X7R allosteric inhibitor reduced cell www.bjbms.org proliferation [16].…”

Section: Introductionmentioning

confidence: 99%

P2X7R as an independent prognostic indicator in gastric cancer

Çalık

Sarikaya

et al. 2020

Bosn J of Basic Med Sci

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Gastric cancer is one of the foremost causes of cancer related death around the world. The P2X7 receptor (P2X7R), a member of the P2X receptor subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers and, recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human gastric cancer specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes [TILs] (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced TNM stage (p < 0.001). Moreover, univariate (HR 3.98; 95% CI 1.89–11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53–12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for gastric cancer.

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High expression of P2X7R is an independent postoperative indicator of poor prognosis in colorectal cancer

Cited by 43 publications

References 16 publications

HMGB1‐RAGE signaling facilitates Ras‐dependent Yap1 expression to drive colorectal cancer stemness and development

HMGB1‐RAGE signaling facilitates Ras‐dependent Yap1 expression to drive colorectal cancer stemness and development

Ethanol upregulates the P2X7 purinergic receptor in human macrophages

P2X7R as an independent prognostic indicator in gastric cancer

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