Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
Eur Rev Med Pharmacol Sci. 2018 Feb;22(3):637-644. doi: 10.26355/eurrev_201802_14288.
Accumulating evidence suggests that SPARC/osteonectin, cwcv, and kazal-like domain proteoglycan 1 (SPOCK1) contributes to the initiation and progression of human cancers. However, little is known about the function mechanisms of SPOCK1 in non-small cell lung cancer (NSCLC). The aim of this study was to investigate the molecular mechanism of SPOCK1 in NSCLC.
The expression levels of SPOCK1 in NSCLC tissues and cell lines were analyzed by qRT-PCR and Western blotting. The proliferative activity of NSCLC cells was determined by MTT and colony formation assays. The transwell assay was used to examine the cell migration and invasive ability. To study the impact of SPOCK1 on Wnt/β‑catenin signaling, we further performed Western blotting for related proteins in this pathway.
We observed that the expression of SPOCK1 at both protein and mRNA levels was also increased in human NSCLC tissues and cell lines. Functionally, down-regulation of SPOCK1 in NSCLC cells markedly suppressed cell proliferation, colony formation, migration and invasion in vitro. Mechanistically, we found that indicated the activation of Wnt/β-catenin pathway was suppressed by SPOCK1 silencing.
The expression of SPOCK1 served as a tumor promoter, possibly through the Wnt/β-catenin signaling pathway in NSCLC. Targeting SPOCK1 could be a potential therapeutic strategy in NSCLC.
越来越多的证据表明，富含半胱氨酸的酸性分泌蛋白（SPARC）/骨粘连蛋白，卷曲螺旋结构域蛋白 1（cwcv）和富含半胱氨酸的 Kazal 型蛋白酶抑制剂 1（SPOCK1）有助于人类癌症的发生和发展。然而，人们对 SPOCK1 在非小细胞肺癌（NSCLC）中的功能机制知之甚少。本研究旨在探讨 SPOCK1 在 NSCLC 中的分子机制。
通过 qRT-PCR 和 Western blot 分析 NSCLC 组织和细胞系中 SPOCK1 的表达水平。MTT 和集落形成实验测定 NSCLC 细胞的增殖活性。Transwell 测定法用于检测细胞迁移和侵袭能力。为了研究 SPOCK1 对 Wnt/β-catenin 信号通路的影响，我们进一步对该通路中的相关蛋白进行了 Western blot 分析。
我们观察到 SPOCK1 的表达在蛋白质和 mRNA 水平上均在人 NSCLC 组织和细胞系中升高。功能上，沉默 SPOCK1 可显著抑制 NSCLC 细胞的体外增殖、集落形成、迁移和侵袭。机制上，我们发现 SPOCK1 沉默抑制了 Wnt/β-catenin 通路的激活。
SPOCK1 的表达作为一种肿瘤促进剂，可能通过 Wnt/β-catenin 信号通路在 NSCLC 中发挥作用。靶向 SPOCK1 可能是 NSCLC 的一种潜在治疗策略。
