title: Tumor necrosis factor receptor 2 promotes growth of colorectal cancer via the PI3K/AKT signaling pathway.
abstract: Tumor necrosis factor receptor 2 (TNFR2) is the receptor for tumor necrosis factor α (TNF-α). TNFR2 differs from tumor necrosis factor 1 (TNFR1) in various ways and is mainly expressed in hematopoietic and endothelial cells. However, studies about its functions in tumors are limited. The contributions of TNFR2 in colorectal cancer (CRC) remain unknown. In the present study, it was found that TNFR2 was positively associated with Ki67 expression in CRC tissues using immunohistochemistry (IHC), and western blot analysis found that Ki67 was upregulated by overexpressing TNFR2 in SW1116 cells and inhibited by silencing TNFR2 in HT29 cells. Methyl thiazolyl tetrazolium assay found that growth of SW1116 cells overexpressing TNFR2 was significantly increased compared with the control group and that the growth of HT29 cells subsequent to silencing TNFR2 was significantly decreased compared with the control group. Clone formation assay found that more clones were formed in SW1116 cells overexpressing TNFR2 than the control group, and less clones formed in HT29 cells subsequent to silencing TNFR2 than the control group. In addition, western blot analysis found that phosphorylation of protein kinase B (AKT) was activated subsequent to overexpressing TNFR2 in SW1116 cells, and inhibited following silencing of TNFR2 in HT29 cells. Additionally, treatment using LY294002 significantly abrogated the promotion of Ki67 expression, growth and clone formation abilities induced by TNFR2 overexpression in SW1116 cells. All the results suggest that TNFR2 can significantly promote CRC growth via the phosphoinositide 3-kinase/AKT signaling pathway; this provides evidential support for taking TNFR2 as a new target for CRC treatment.
authors.affiliation: Oncology Department, Second People's Hospital of Dongying City, Dongying, Shandong 257335, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhao
authors.affiliation: Department of Medical Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250017, P.R. China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Li
authors.affiliation: Second Department of Liver Failure, 302 Hospital of PLA, Beijing 100000, P.R. China.
authors.forename: Zifeng
authors.initials: Z
authors.lastname: Liu
keywords: colorectal cancer; proliferation; tumor necrosis factor receptor 2