scholarly journals Tumor-associated calcium signal transducer 2 regulates neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway

Tumor Biology ◽  
2017 ◽  
Vol 39 (3) ◽  
pp. 101042831769432 ◽  
Author(s):  
Xiaobin Guo ◽  
Xiaoming Zhu ◽  
Limin Zhao ◽  
Xiao Li ◽  
Dongjun Cheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Calcium Signal ◽  
Small Cell Lung

Lung cancer, especially the non-small-cell lung cancer, is a highly aggressive vascular cancer with excessively activated signaling pathways. Tumor-associated calcium signal transducer 2, also known as trop2, was identified to be correlated with tumor proliferation and invasion of non-small-cell lung cancer; however, the biological role of trop2 in neovascularization of non-small-cell lung cancer remained elusive. In this study, we first verified that trop2 was overexpressed in non-small-cell lung cancer tissues as well as cell lines and that the increased expression of trop2 promoted non-small-cell lung cancer cell proliferation and invasion. Then, we expanded the biological role of trop2 by in vitro and in vivo angiogenesis assay. The tubular formation analysis revealed that trop2 promoted non-small-cell lung cancer angiogenesis in vitro, and the immunohistochemistry staining of vascular markers (CD31 and CD34) provided evidences that trop2 promoted in vivo neovascularization. The results of polymerase chain reaction array revealed that trop2 promoted the expression level of two well-known angiogenesis factors MMP13 and PECAM1. By screening the trop2-related signaling pathways, we observed that excessive angiogenesis was correlated with activation of ERK1/2 signaling pathway, and ERK1/2 inhibitor (U0126) could suppress the tubular formation ability induced by trop2 expression. These results suggested that trop2 facilitated neovascularization of non-small-cell lung cancer via activating ERK1/2 signaling pathway. Targeting trop2 might provide novel anti-angiogenesis strategy for non-small-cell lung cancer treatment.

scholarly journals KPNB1-mediated nuclear translocation of PD-L1 promotes non-small cell lung cancer cell proliferation via the Gas6/MerTK signaling pathway

2020 ◽  
Author(s):  
Wenwen Du ◽  
Jianjie Zhu ◽  
Yuanyuan Zeng ◽  
Ting Liu ◽  
Yang Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Small Cell Lung

Abstract In addition to the role of programmed cell death ligand 1 (PD-L1) in facilitating tumour cells escape from immune surveillance, it is considered as a crucial effector in transducing intrinsic signals to promote tumour development. Our previous study has pointed out that PD-L1 promotes non-small cell lung cancer (NSCLC) cell proliferation, but the mechanism remains elusive. Here we first demonstrated that PD-L1 expression levels were positively correlated with p-MerTK levels in patient samples and NSCLC cell lines. In addition, PD-L1 knockdown led to the reduced phosphorylation level of MerTK in vitro. We next showed that PD-L1 regulated NSCLC cell proliferation via Gas6/MerTK signaling pathway in vitro and in vivo. To investigate the underlying mechanism, we unexpectedly found that PD-L1 translocated into the nucleus of cancer cells which was facilitated through the binding of Karyopherin β1 (KPNB1). Nuclear PD-L1 (nPD-L1), coupled with transcription factor Sp1, regulated the synthesis of Gas6 mRNA and promoted Gas6 secretion to activate MerTK signaling pathway. Taken together, our results shed light on the novel role of nPD-L1 in NSCLC cell proliferation and reveal a new molecular mechanism underlying nPD-L1-mediated Gas6/MerTK signaling activation. All above findings provide the possible combinational implications for PD-L1 targeted immunotherapy in the clinic.

scholarly journals CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Hang Li ◽  
Jun Che ◽  
Mian Jiang ◽  
Ming Cui ◽  
Guoxing Feng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Estrogen Receptor ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Target Genes ◽  
Small Cell ◽  
Small Cell Lung

Abstract Introduction Radioresistance is a major challenge in lung cancer radiotherapy, and new radiosensitizers are urgently needed. Estrogen receptor β (ERβ) is involved in the progression of non-small cell lung cancer (NSCLC), however, the role of ERβ in the response to radiotherapy in lung cancer remains elusive. In the present study, we investigated the mechanism underlying ERβ-mediated transcriptional activation and radioresistance of NSCLC cells. Methods Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of CLPTM1L, ERβ and other target genes. The mechanism of CLPTM1L in modulation of radiosensitivity was investigated by chromatin immunoprecipitation assay, luciferase reporter gene assay, immunofluorescence staining, confocal microscopy, coimmunoprecipitation and GST pull-down assays. The functional role of CLPTM1L was detected by function assays in vitro and in vivo. Results CLPTM1L expression was negatively correlated with the radiosensitivity of NSCLC cell lines, and irradiation upregulated CLPTM1L in radioresistant (A549) but not in radiosensitive (H460) NSCLC cells. Meanwhile, IR induced the translocation of CLPTM1L from the cytoplasm into the nucleus in NSCLC cells. Moreover, CLPTM1L induced radioresistance in NSCLC cells. iTRAQ-based analysis and cDNA microarray identified irradiation-related genes commonly targeted by CLPTM1L and ERβ, and CLPTM1L upregulated ERβ-induced genes CDC25A, c-Jun, and BCL2. Mechanistically, CLPTM1L coactivated ERβ by directly interacting with ERβ through the LXXLL NR (nuclear receptor)-binding motif. Functionally, ERβ silencing was sufficient to block CLPTM1L-enhanced radioresistance of NSCLC cells in vitro. CLPTM1L shRNA treatment in combination with irradiation significantly inhibited cancer cell growth in NSCLC xenograft tumors in vivo. Conclusions The present results indicate that CLPTM1L acts as a critical coactivator of ERβ to promote the transcription of its target genes and induce radioresistance of NSCLC cells, suggesting a new target for radiosensitization in NSCLC therapy.

Hsa_circ_0003288 facilitates tumor progression by targeting miR-145 in non–small cell lung cancer cells

2021 ◽  
pp. 1-9
Author(s):  
Li-Na Pan ◽  
Yun-Fang Ma ◽  
Jia-An Hu ◽  
Zhi-Hong Xu
Keyword(s):  
Lung Cancer ◽  
Cell Proliferation ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung

Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo. Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC.

scholarly journals Expression of CDCA7 Is a Prognostic Biomarker and Potential Therapeutic Target in Non-small Cell Lung Cancer 

2021 ◽  
Author(s):  
wen yuan ◽  
Wenhui Zeng ◽  
Haiyan Tan ◽  
Muhammad Jamal ◽  
Tian Xie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Therapeutic Target ◽  
Small Cell ◽  
Small Cell Lung ◽  
Tumor Tissues

Abstract BackgroundCell Division Cycle Associated 7 (CDCA7) was first identified as a direct target gene of c-Myc and dysregulated in various types of human cancer. However, it has limited implication in non-small Cell Lung Cancer (NSCLC). We aimed to explore the critical role of CDCA7 in NSCLC.Methods In this study, we identified CDCA7 upregulation and association with the prognosis of NSCLC by integrating analysis of 3 Gene Expression Omnibus (GEO) databases. Real-time PCR and immunohistochemistry (IHC) were used to determine collected clinical NSCLC samples. Chi-square test was used to examine possible correlations between CDCA7 expression and clinicopathological factors. Univariate and multivariate Cox proportional hazards regression analysis were performed to determine whether CDCA7 is an independent risk factor for overall survival (OS). The effect of CDCA7 expression on proliferation, cell cycle and apoptosis ability of NSCLC cells was detected by cell counting kit-8 (CCK-8) and flow cytometry. CDCA7 stably knocking down cell line was established and Western blotting assay was applied to measure relevant protein expression. Xenograft models were used to examine the role of CDCA7 on tumorigenicity of NSCLC cells.Results Analysis of clinical samples confirmed the CDCA7 high expression in tumor tissues compared with adjacent non-tumor tissues and predicted shorter OS time. COX proportional risk model analysis showed that the expression levels of CDCA7 was independent prognostic factors. We observed that CDCA7 silencing efficiently affect the proliferation, apoptosis and cycle distribution of NSCLC cells in vitro. Further results demonstrated that the expression of CDCA7 in A549/DDP cells was significantly higher than that in A549 cells, CDCA7 silencing efficiently down regulation cisplatin sensitivity in A549/DDP cells. Importantly, the depletion of CDCA7 strongly reduced the tumorigenicity of NSCLC cells in vivo. Furthermore, depletion of CDCA7 expression markedly affected the expression of cell division protein kinase 6 (CDK6) and caspase7 both in vitro and in vivo. In vitro study, we showed that CDCA7 silencing promotes A549 apoptosis via extracellular regulated protein kinases (ERK) pathway.ConclusionHighly expressed CDCA7 plays a crucial role in the pathogenesis of NSCLC and might be a potential prognostic factor and therapeutic target in NSCLC.

Down-regulation of lncRNA XIST inhibits cell proliferation via regulating miR-744/RING1 axis in non-small cell lung cancer

2019 ◽  
Vol 133 (14) ◽  
pp. 1567-1579 ◽  
Author(s):  
Jinglu Wang ◽  
Haibo Cai ◽  
Zhaoxia Dai ◽  
Gang Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Tumor Progression ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lncrna Xist

Abstract Long non-coding RNAs (lncRNAs) are known to be potential factors in promoting tumor progression. However, the function and mechanism of lncRNA XIST in non-small cell lung cancer (NSCLC) remains poorly understood. The expression levels of lncRNA XIST in NSCLC tissues and cell lines were detected with real-time PCR, and the correlation of the expression level of XIST with histopathological characteristics and prognosis was analyzed. The biological function of lncRNA XIST was validated through assays in vivo and in vitro. The expression of lncRNA XIST was significantly up-regulated in NSCLC tissues. In addition, overexpression of XIST was positively correlated with the advanced clinical status of tumors, as well as poor overall survival and DFS. A tumor suppressive effect was presented via functional knockdown of lncRNA XIST. Up-regulation of XIST enhanced the proliferation, migration, and invasion ability of NSCLC cells both in vivo and in vitro. Mechanically, it was indicated that XIST could serve as an endogenous competitive RNA modulating miR-744, leading to the miR-744/RING1 signaling pathway inhibition and Wnt/β-catenin signaling pathway activation. Taken together, it was confirmed here that XIST overexpression is associated with tumor progression phenotype and the newly discovered XIST/miR-744/RING1 axis, which could serve as a potential biomarker and therapeutic target for NSCLC.

Sign in / Sign up

Export Citation Format

Share Document