SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade

Cancer Cell International

Yingying Zheng¹  Shaoqiang Wang²  Zhiwei He³  Chunfang Zhang³  Wolong Zhou³  Yuanda Cheng³ 

[1] Department of Endocrinology, Affiliated Hospital of Jining Medical University, Jining Medical University;Department of Thoracic Surgery, Affiliated Hospital of Jining Medical University, Jining Medical University;Department of Thoracic Surgery, Xiangya Hospital, Central South University;

关键词: SH2B1;    Proliferation;    AKT;    NSCLC;   

DOI  :  10.1186/s12935-018-0632-x

来源: DOAJ

【 摘 要 】

Abstract Background 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. Methods 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. Results 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. Conclusions 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.

【 授权许可】

Unknown