C-X-C chemokine receptor 2 correlates with unfavorable prognosis and facilitates malignant cell activities via activating JAK2/STAT3 pathway in non-small cell lung cancer

Lin, Wei; Liu, Yugang; Ma, Yuefeng; Ding, Chao; Zhang, Huijun; Lu, Zixing; Gu, Zhenning; Zhu, Changsheng

doi:10.1080/15384101.2019.1689471

Cited by 18 publications

(12 citation statements)

References 28 publications

(33 reference statements)

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“…Targeting CXCR1/2 prevented JAK2 and STAT3 phosphorylation, consistent with the observations of Wei et al. ( 32 ). These findings are in line with our prior studies confirming that inhibition of CXCR2 signalling potentiated oxaliplatin-induced apoptosis in PC3 cells ( 23 ).…”

Section: Discussionsupporting

confidence: 90%

“…Interestingly, inhibition of CXCR1/2 signalling in vitro did not modulate the magnitude of DNA foci formation or the rate of DNA repair in these cells. Recent research has confirmed that elevated CXCR2 expression can facilitate unfavourable prognosis and tumourigenesis via activation of the JAK2/STAT3 pathway ( 32 ). Our data suggest that radiation-induced CXCR1/2 signalling sustains the viability of PTEN -depleted cells using this exact mechanism.…”

Section: Discussionmentioning

confidence: 99%

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Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma

et al. 2020

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Abstract Functional impairment of the tumour suppressor PTEN is common in primary prostate cancer and has been linked to relapse post-radiotherapy (post-RT). Pre-clinical modelling supports elevated CXC chemokine signalling as a critical mediator of PTEN-depleted disease progression and therapeutic resistance. We assessed the correlation of PTEN deficiency with CXC chemokine signalling and its association with clinical outcomes. Gene expression analysis characterized a PTENLOW/CXCR1HIGH/CXCR2HIGH cluster of tumours that associates with earlier time to biochemical recurrence [hazard ratio (HR) 5.87 and 2.65, respectively] and development of systemic metastasis (HR 3.51). In vitro, CXCL signalling was further amplified following exposure of PTEN-deficient prostate cancer cell lines to ionizing radiation (IR). Inhibition of CXCR1/2 signalling in PTEN-depleted cell-based models increased IR sensitivity. In vivo, administration of a CXCR1/2-targeted pepducin (x1/2pal-i3), or CXCR2-specific antagonist (AZD5069), in combination with IR to PTEN-deficient xenografts attenuated tumour growth and progression compared to control or IR alone. Post-mortem analysis confirmed that x1/2pal-i3 administration attenuated IR-induced CXCL signalling and anti-apoptotic protein expression. Interventions targeting CXC chemokine signalling may provide an effective strategy to combine with RT in locally advanced prostate cancer patients with known presence of PTEN-deficient foci.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma

et al. 2020

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“…In brief, the rabbit anti-p60 katanin antibody (Abcam, USA) at 1:20 dilution and goat anti-rabbit IgG H&L (HRP) (Abcam, USA) at 1:50,000 dilution were used as primary antibody and secondary antibody, respectively, in the IHC staining. All IHC procedures were performed as described in a previous study [13]. Finally, the expression of katanin P60 in tissue specimen was assessed by IHC score, which was obtained using a semi-quantitative scoring method as previously described [14].…”

Section: Ihc Stainingmentioning

confidence: 99%

Katanin P60: a potential biomarker for lymph node metastasis and prognosis for non-small cell lung cancer

2020

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Background: This study aimed to assess the correlation of katanin P60 expression with clinical characteristics and survival profiles of surgical non-small cell lung cancer (NSCLC) patients. Methods: Two hundred and sixty-five primary NSCLC patients treated by surgical resection were retrospectively viewed. The expression of katanin P60 in the tumor specimen was detected by the immunohistochemical (IHC) staining assay. Preoperative clinical data were collected from patients' medical records, and survival data were extracted from follow-up records. Results: There were 127 (47.9%) and 138 (52.1%) patients with katanin P60-low expression and-high expression, respectively; in addition, patients presenting katanin P60-high+,-high++, and-high+++ expression were 62 (23.4%), 63 (23.8%), and 13 (4.9%), respectively. Katanin P60 expression was correlated with lymph node (LYN) metastasis and advanced TNM stage but not pathological grade, tumor size, carcinoembryonic antigen (CEA) level or other non-tumor features in NSCLC patients. Regarding survival profiles, disease-free survival (DFS) and overall survival (OS) were both the lowest in katanin P60-high+++ expression patients, followed with katanin P60-high++ patients, katanin P60-high+ patients, and the highest in katanin P60-low expression patients. Further analysis illustrated that katanin P60-high expression was an independent predictive factor for unfavorable DFS and OS in NSCLC patients. Conclusions: Katanin P60 presents potential as a biomarker for lymph node metastasis and prognosis in NSCLC patients.

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“…Membrane-bound forms of chemokines allow communication with their receptors through direct cell-cell contact, which influences multiple fundamental biological processes and disease conditions, including cancer [ 77 ]. C-X-C chemokine receptor 2 ( CXCR2 ) is a key chemokine receptors that has been shown to promote NSCLC cell proliferation, invasion, and stemness while suppressing apoptosis and chemosensitivity, via activating JAK2/STAT3 signaling [ 78 ]. (3) The structural modeling showed that both GNG11 and chemokines in chemokine signaling pathway are not druggable, but GNG11 could form stable physical interactions with CXCR2 (DS = 0.834), CXCL3 (DS = 0.721), and PPBP (DS = 0.85) by a series of interfacial residues, which may offer more promising hotspots for drug targeting.…”

Section: Discussionmentioning

confidence: 99%

Knowledge-Guided “Community Network” Analysis Reveals the Functional Modules and Candidate Targets in Non-Small-Cell Lung Cancer

Wang

Han

Yang

et al. 2021

Cells

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Non-small-cell lung cancer (NSCLC) represents a heterogeneous group of malignancies that are the leading cause of cancer-related death worldwide. Although many NSCLC-related genes and pathways have been identified, there remains an urgent need to mechanistically understand how these genes and pathways drive NSCLC. Here, we propose a knowledge-guided and network-based integration method, called the node and edge Prioritization-based Community Analysis, to identify functional modules and their candidate targets in NSCLC. The protein–protein interaction network was prioritized by performing a random walk with restart algorithm based on NSCLC seed genes and the integrating edge weights, and then a “community network” was constructed by combining Girvan–Newman and Label Propagation algorithms. This systems biology analysis revealed that the CCNB1-mediated network in the largest community provides a modular biomarker, the second community serves as a drug regulatory module, and the two are connected by some contextual signaling motifs. Moreover, integrating structural information into the signaling network suggested novel protein–protein interactions with therapeutic significance, such as interactions between GNG11 and CXCR2, CXCL3, and PPBP. This study provides new mechanistic insights into the landscape of cellular functions in the context of modular networks and will help in developing therapeutic targets for NSCLC.

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C-X-C chemokine receptor 2 correlates with unfavorable prognosis and facilitates malignant cell activities via activating JAK2/STAT3 pathway in non-small cell lung cancer

Abstract: Zhu (2019) C-X-C chemokine receptor 2 correlates with unfavorable prognosis and facilitates malignant cell activities via activating JAK2/STAT3 pathway in non-small cell lung cancer,

Cited by 18 publications

References 28 publications

Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma

Clinical and functional characterization of CXCR1/CXCR2 biology in the relapse and radiotherapy resistance of primary PTEN-deficient prostate carcinoma

Katanin P60: a potential biomarker for lymph node metastasis and prognosis for non-small cell lung cancer

Knowledge-Guided “Community Network” Analysis Reveals the Functional Modules and Candidate Targets in Non-Small-Cell Lung Cancer

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