HES5 promotes cellular proliferation of non-small cell lung cancer through STAT3 signaling

Gu,Shudong; Zhang,Rui; Gu,Jun; Li,Xia; Lv,Liting; Jiang,Jingting; Xu,Zhen; Wang,Shuo; Shi,Cui; Wang,Dan Ping; Wu,Changping

doi:10.3892/or.2016.5268

HES5 promotes cellular proliferation of non-small cell lung cancer through STAT3 signaling

Authors:
- Shudong Gu
- Rui Zhang
- Jun Gu
- Xia Li
- Liting Lv
- Jingting Jiang
- Zhen Xu
- Shuo Wang
- Cui Shi
- Dan Ping Wang
- Changping Wu
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Affiliations: Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Department of Respiratory, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China
Published online on: November 22, 2016 https://doi.org/10.3892/or.2016.5268
Pages: 474-482

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Abstract

HES5 is a transcription factor activated downstream of the Notch pathway and regulates cell differentiation in multiple tissues. Disruption of its normal expression has been associated with developmental diseases and cancer. But its role in non-small cell lung cancer (NSCLC) remains elusive. Western blot analysis and immunohistochemistry assays demonstrated that HES5 expression was frequently increased in NSCLC tumor tissues and cell lines. Moreover, immunohistochemistry analysis revealed that upregulation of HES5 expression was positively correlated with a more invasive tumor phenotype and poor prognosis. Immunoprecipitation assay indicated that HES5 directly interacted with STAT3. In addition, depletion of HES5 resulted in inhibited phosphorylation of STAT3 and decreased expression of the downstream genes. In vitro studies, using serum starvation-refeeding experiment and HES5-siRNA transfection assay demonstrated that HES5 expression promoted proliferation of NSCLC cells, while HES5 knockdown caused growth arrest of cell cycle at G0/G1 phase, decreased rate of colony formation and alleviated cellular apoptosis. Taken together, out data have delineated that HES5 might contribute to the proliferation of NSCLC by STAT3 signaling.

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