SOSTDC1 is down-regulated in non-small cell lung cancer and contributes to cancer cell proliferation.
SOSTDC1 is down-regulated in non-small cell lung cancer and contributes to cancer cell proliferation.
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SOSTDC1 在非小细胞肺癌中下调，有助于癌细胞增殖。
DOI：
10.1186/s13578-016-0091-9
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发表时间：
2016
影响因子：
7.5
通讯作者：
Guan H
中科院分区：
文献类型：
--
作者：
Liu L;Wu S;Yang Y;Cai J;Zhu X;Wu J;Li M;Guan H
非小细胞肺癌（NSCLC）是全世界最常诊断和致命的癌症。含硬化蛋白结构域的蛋白 1 (SOSTDC1) 已被发现在多种类型的癌症中具有肿瘤抑制作用。然而，SOSTDC1在NSCLC中的表达水平和生物学功能仍不清楚。我们目前的研究旨在确定 SOSTDC1 在 NSCLC 中的生物学意义。我们发现 SOSTDC1 在 NSCLC 中显着下调。此外，SOSTDC1表达较高的患者预后明显好于SOSTDC1表达较低的患者。体外 MTT、集落形成、软琼脂和 EdU 掺入测定显示，NSCLC 细胞系 A549 和 NCI-H520 中 SOSTDC1 的异位表达可以抑制增殖。此外，与体内载体对照细胞相比，稳定表达异位SOSTDC1的A549细胞生长更慢，形成的肿瘤更小。机制研究表明，SOSTDC1 过表达导致 p21Cip 和 p27Kip 水平升高，从而降低 Rb 磷酸化状态和 E2F 转录活性。 SOSTDC1 在 NSCLC 中表达下调，其表达水平可指示该疾病患者的临床结果。 SOSTDC1 可能是一种肿瘤抑制因子，通过调节 p21Cip 和 p27Kip 抑制 NSCLC 细胞的增殖，进而影响 Rb-E2F 信号传导。
Non-small cell lung cancer (NSCLC) is the most commonly diagnosed and fatal cancer worldwide. Sclerostin domain containing protein 1 (SOSTDC1) has been found to be tumor-suppressive in several types of cancers. However, the expression level and biological functions of SOSTDC1 in NSCLC remain unknown. Our current study aimed to identify the biological significance of SOSTDC1 in NSCLC. We found that SOSTDC1 was significantly down-regulated in NSCLC. Moreover, patients with higher expression of SOSTDC1 had a significant better prognosis than those with lower SOSTDC1 expression. Ectopic expression of SOSTDC1 in NSCLC cell lines A549 and NCI-H520 could inhibit proliferation as shown by MTT, colony formation, soft agar and EdU incorporation assays in vitro. Furthermore, A549 cells stably expressing ectopic SOSTDC1 grew more slowly and formed smaller tumors than vector-control cells in vivo. Mechanistic studies demonstrated that SOSTDC1 over-expression led to increased p21Cip and p27Kip levels, thereby decreasing Rb phosphorylation status and E2F transcription activity. SOSTDC1 is down-regulated in NSCLC, and its expression level is indicative of clinical outcome of patients with the disease. SOSTDC1 might represent a tumor suppressor through inhibiting the proliferation of NSCLC cells by regulating p21Cip and p27Kip, which in turn affects Rb-E2F signaling.