Wang Shaoqiang, Zheng Yingying, He Zhiwei, Zhou Wolong, Cheng Yuanda, Zhang Chunfang
1Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029 Shandong People's Republic of China.
2Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272029 Shandong People's Republic of China.
Cancer Cell Int. 2018 Sep 6;18:132. doi: 10.1186/s12935-018-0632-x. eCollection 2018.
Non-small cell lung cancer (NSCLC), the most prevalent type of human lung cancer, is characterized by many molecular abnormalities. SH2B1, a member of the SH2-domain containing family, have recently been shown to act as tumor activators in multiple cancers. The objective of this study was to investigate the role SH2B1 and the underlying molecular mechanism in NSCLC.
Cell functional analysis and cell line-derived xenograft model were performed to determine SH2B1 potential roles on NSCLC cell proliferation in vitro and in vivo. In vitro assays were performed to identify signal molecular mechanisms. Subsequently, 104 patients with NSCLC undergoing primary surgical resection were recruited to evaluated expression of SH2B1 and Akt/mTOR signaling markers by immunohistochemical staining to determine their clinicopathologic significance.
Modulation of SH2B1 expression levels had distinct effects on cell proliferation, cell cycle and apoptosis in the NSCLC cell lines A549 and H1299. At the molecular level, overexpression of SH2B1 resulted in the upregulation of the Akt/mTOR markers, p-Akt and p-mTOR, and downregulation of PTEN to promote NSCLC cell proliferation, while silencing SH2B1 had the opposite effect. In human NSCLC specimens, SH2B1 expression levels were positively associated with Akt/mTOR signaling pathway markers.
The SH2B1/Akt/mTOR/PTEN axis is required for regulating NSCLC cell proliferation and might prove to be a promising strategy for restraining tumor progression in NSCLC patients.
非小细胞肺癌（NSCLC）是人类肺癌中最常见的类型，具有许多分子异常特征。SH2B1是含SH2结构域家族的成员之一，最近已被证明在多种癌症中作为肿瘤激活因子发挥作用。本研究的目的是探讨SH2B1在NSCLC中的作用及其潜在分子机制。
进行细胞功能分析和细胞系来源的异种移植模型，以确定SH2B1在体外和体内对NSCLC细胞增殖的潜在作用。进行体外试验以鉴定信号分子机制。随后，招募104例接受原发性手术切除的NSCLC患者，通过免疫组织化学染色评估SH2B1和Akt/mTOR信号标志物的表达，以确定其临床病理意义。
调节SH2B1表达水平对NSCLC细胞系A549和H1299的细胞增殖、细胞周期和凋亡有不同影响。在分子水平上，SH2B1的过表达导致Akt/mTOR标志物p-Akt和p-mTOR上调，PTEN下调，从而促进NSCLC细胞增殖，而沉默SH2B1则产生相反效果。在人NSCLC标本中，SH2B1表达水平与Akt/mTOR信号通路标志物呈正相关。
SH2B1/Akt/mTOR/PTEN轴是调节NSCLC细胞增殖所必需的，可能被证明是抑制NSCLC患者肿瘤进展的一种有前景的策略。
