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SRPX2 promotes cell proliferation and invasion via activating FAK/SRC/ERK pathway in non-small cell lung cancer.

SRPX2 通过激活 FAK/SRC/ERK 通路促进非小细胞肺癌细胞增殖和侵袭。

  • 影响因子:1.68
  • DOI:10.18388/abp.2020_5158
  • 作者列表:"Li X","Liu J","Sun H","Zou Y","Chen J","Chen Y","Chen C","Wu X
  • 发表时间:2020-06-18
Abstract

BACKGROUND:Recent studies showed that sushi repeat containing protein X linked 2 (SRPX2) could participate in the development of various malignant tumors. However, its role in non-small cell lung cancer (NSCLC) was unknown. The aim of the study was to prospectively investigate the role of SRPX2 in NSCLC cell proliferation, migration and invasion and reveal the underlying mechanism. MATERIAL AND METHODS:Quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunohistochemistry - IHC) were used to measure detect the mRNA and protein levels, respectively, in NSCLC tissues and cell lines. Cell Counting Kit-8 (CCK-8), colony formation, wound healing and transwell assays were utilized to assess cell proliferation, migration and invasion. In vivo subcutaneous xenograft tumor model was established to detect the tumorigenic function of SRPX2, and IHC assay was performed to measure protein expression. RESULTS:SRPX2 expression was upregulated in NSCLC tissues and cell lines, and positively correlated with tumor size, lymph node metastasis, distant metastasis and clinical stage. High SRPX2 expression also predicted poor prognosis. In vitro experiments indicated that overexpression of SRPX2 promoted the proliferation, migration, and invasion of SPC-A1 cells while knockdown of SRPX2 caused the opposite effects in A549 cells. Specifically, SRPX2 activated FAK/SRC/ERK pathway and its downstream effectors and promoted epithelial-mesenchymal transition (EMT). CONCLUSION:Taken together, our findings revealed a functional role of SRPX2 in NSCLC cell proliferation, migration and invasion. The underlying mechanism was, at least partially, the activation of FAK/SRC/ERK pathway. This study provides the molecular basis for targeting SRPX2 in potential clinical application for NSCLC.

摘要

背景: 最近的研究表明,含有 X 连接蛋白 2 (SRPX2) 的寿司重复序列可参与多种恶性肿瘤的发生发展。然而,其在非小细胞肺癌 (NSCLC) 中的作用尚不清楚。本研究的目的是前瞻性研究 SRPX2 在 NSCLC 细胞增殖、迁移和侵袭中的作用,并揭示其潜在的机制。 材料和方法: 采用定量实时聚合酶链反应 (qRT-PCR) 、 western blot 和免疫组织化学 (IHC) 分别检测 mRNA 和蛋白水平,在 NSCLC 组织和细胞系中。细胞计数试剂盒-8 (CCK-8) 、集落形成、伤口愈合和 transwell 试验用于评估细胞增殖、迁移和侵袭。建立体内皮下异种移植肿瘤模型检测 SRPX2 的致瘤功能,IHC 法测定蛋白表达。 结果: SRPX2 在 NSCLC 组织和细胞系中表达上调,且与肿瘤大小、淋巴结转移、远处转移及临床分期呈正相关。SRPX2 高表达也预示预后不良。体外实验表明,SRPX2 的过表达促进了 SPC-A1 细胞的增殖、迁移和侵袭,而敲除 SRPX2 则引起了 A549 细胞的相反作用。具体而言,SRPX2 激活 FAK/SRC/ERK 通路及其下游效应因子,促进上皮间质转化 (EMT)。 结论: 总之,我们的研究结果揭示了 SRPX2 在 NSCLC 细胞增殖、迁移和侵袭中的功能作用。潜在的机制至少部分是 FAK/SRC/ERK 通路的激活。本研究为靶向 SRPX2 治疗 NSCLC 的潜在临床应用提供了分子基础。

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影响因子:1.84
发表时间:2020-01-01
来源期刊:Oncology letters
DOI:10.3892/ol.2019.11149
作者列表:["Das SK","Huang YY","Li B","Yu XX","Xiao RH","Yang HF"]

METHODS::The aim of the present study was to compare the safety and efficacy of cryoablation (CA) and microwave ablation (MWA) as treatments for non-small cell lung cancer (NSCLC). Patients with stage IIIB or IV NSCLC treated with CA (n=45) or MWA (n=56) were enrolled in the present study. The primary endpoint was progression-free survival (PFS); the secondary endpoints included overall survival (OS) time and adverse events (AEs). The median PFS times between the two groups were not significantly different (P=0.36): CA, 10 months [95% confidence interval (CI), 7.5-12.4] vs. MWA, 11 months (95% CI, 9.5-12.4). The OS times between the two groups were also not significantly different (P=0.07): CA, 27.5 months (95% CI, 22.8-31.2 months) vs. MWA, 18 months (95% CI, 12.5-23.5). For larger tumors (>3 cm), patients treated with MWA had significantly longer median PFS (P=0.04; MWA, 10.5 months vs. CA, 7.0 months) and OS times (P=0.04; MWA, 24.5 months vs. CA, 14.5 months) compared patients treated with CA. However, for smaller tumors (≤3 cm), median PFS (P=0.79; MWA, 11.0 months vs. CA, 13.0 months) and OS times (P=0.39; MWA, 30.0 months vs. CA, 26.5 months) between the two groups did not differ significantly. The incidence rates of AEs were similar in the two groups (P>0.05). The number of applicators, tumor size and length of the lung traversed by applicators were associated with a higher risk of pneumothorax and intra-pulmonary hemorrhage in the two groups. Treatment with CA resulted in significantly less intraprocedural pain compared with treatment with MWA (P=0.001). Overall, the present study demonstrated that CA and MWA were comparably safe and effective procedures for the treatment of small tumors. However, treatment with MWA was superior compared with CA for the treatment of large tumors.

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影响因子:8.44
发表时间:2020-02-01
DOI:10.1016/j.annonc.2019.10.022
作者列表:["Mazieres J","Cropet C","Montané L","Barlesi F","Souquet PJ","Quantin X","Dubos-Arvis C","Otto J","Favier L","Avrillon V","Cadranel J","Moro-Sibilot D","Monnet I","Westeel V","Le Treut J","Brain E","Trédaniel J","Jaffro M","Collot S","Ferretti GR","Tiffon C","Mahier-Ait Oukhatar C","Blay JY"]

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