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

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.


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。



作者列表:["Esme H","Can A","Şehitogullari A"]

METHODS:BACKGROUND:The objectives of this study are to assess the chest drainage volumes of patients undergoing anatomic resection of non-small cell lung carcinoma and to determine the safety and effectiveness of administering enoxaparin for thromboprophylaxis. METHODS:A total of 77 patients were included in the study. A study was conducted on the first group of 42 patients in which enoxaparin prophylaxis (enoxaparin, 40 mg) was subcutaneously injected once a day for a period of three days after the patients underwent anatomic pulmonary resection between March 2016 and March 2018. An enoxaparin-free group was identified and included 35 patients who received no enoxaparin prophylaxis after undergoing anatomic pulmonary resection between February 2013 and February 2016. We compared the changes in hemoglobin (Hb) levels, postoperative 3-day drainage volume, transfusion volume, pulmonary complications and length of stay between the two groups. RESULTS:No differences in postoperative Hb levels, chest drainage volume, transfusion volume, postoperative complications, and length of stay were observed between the two groups. Deep-vein thrombosis was noted in a patient in the enoxaparin-free group. No major bleeding was noted in either group. CONCLUSION:We found that for patients undergoing anatomic resection of primary lung cancer, the blood transfusion and chest drainage volumes did not differ, regardless of whether the patients were given enoxaparin. To the best of our knowledge, the impact of low-molecular-weight heparin on chest tube drainage volume for patients undergoing anatomic resection of non-small cell lung carcinoma has not been investigated before.

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来源期刊:Oncology letters
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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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"]

METHODS:BACKGROUND:BRAF mutations occurring in 1%-5% of patients with non-small-cell lung cancer (NSCLC) are therapeutic targets for these cancers but the impact of the exact mutation on clinical activity is unclear. The French National Cancer Institute (INCA) launched the AcSé vemurafenib trial to assess the efficacy and safety of vemurafenib in cancers with various BRAF mutations. We herein report the results of the NSCLC cohort. PATIENTS AND METHODS:Tumour samples were screened for BRAF mutations in INCA-certified molecular genetic centres. Patients with BRAF-mutated tumours progressing after ≥1 line of treatment were proposed vemurafenib 960 mg twice daily. Between October 2014 and July 2018, 118 patients were enrolled in the NSCLC cohort. The primary outcome was the objective response rate (ORR) assessed every 8 weeks (RECIST v1.1). A sequential Bayesian approach was planned with an inefficacy bound of 10% for ORR. If no early stopping occurred, the treatment was of interest if the estimated ORR was ≥30% with a 90% probability. Secondary outcomes were tolerance, response duration, progression-free survival (PFS), and overall survival (OS). RESULTS:Of the 118 patients enrolled, 101 presented with a BRAFV600 mutation and 17 with BRAFnonV600 mutations; the median follow-up was 23.9 months. In the BRAFnonV600 cohort, no objective response was observed and this cohort was stopped. In the BRAFV600 cohort, 43/96 patients had objective responses. The mean Bayesian estimated success rate was 44.9% [95% confidence intervals (CI) 35.2%-54.8%]. The ORR had a 99.9% probability of being ≥30%. Median response duration was 6.4 months, median PFS was 5.2 months (95% CI 3.8-6.8), and OS was 10 months (95% CI 6.8-15.7). The vemurafenib safety profile was consistent with previous publications. CONCLUSION:Routine biomarker screening of NSCLC should include BRAFV600 mutations. Vemurafenib monotherapy is effective for treating patients with BRAFV600-mutated NSCLC but not those with BRAFnonV600 mutations. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT02304809.

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