Translationally controlled tumor protein affects colorectal cancer metastasis through the high mobility group box 1-dependent pathway

Huang,Maoliang; Geng,Yan; Deng,Qiaoting; Li,Ru; Shao,Xiangyang; Zhang,Zhigao; Xu,Weiwen; Wu,Yingsong; Ma,Qiang

doi:10.3892/ijo.2018.4502

Translationally controlled tumor protein affects colorectal cancer metastasis through the high mobility group box 1-dependent pathway

Authors:
- Maoliang Huang
- Yan Geng
- Qiaoting Deng
- Ru Li
- Xiangyang Shao
- Zhigao Zhang
- Weiwen Xu
- Yingsong Wu
- Qiang Ma
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Affiliations: Fuzhou Dingxiang Clinic, Fuzhou, Fujian 350028, P.R. China, Department of Intensive Care Unit, 303 Hospital of Chinese People's Liberation Army, Nanning, Guanxi 530021, P.R. China, Institute of Antibody Engineering, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Published online on: July 25, 2018 https://doi.org/10.3892/ijo.2018.4502
Pages: 1481-1492
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Recently, accumulating evidence from clinical and experimental researches have suggested that translationally controlled tumor protein (TCTP) and high mobility group box 1 (HMGB1) are implicated in colorectal cancer (CRC) metastasis. However, whether there is an interconnection between these two tumor-promoting proteins and how they affect CRC metastasis remain to be fully elucidated. In the present study, the expression level of TCTP in CRC tissues was assessed by immunohistochemical staining and immunoblotting, and the serum concentration of HMGB1 in patients with CRC was detected by enzyme-linked immunosorbent assay. In vitro, following the modulation of TCTP expression in colon cancer LoVo cells, the translocation behavior of HMGB1 was observed by immunofluorescence assay. Furthermore, the activity of nuclear factor-κB (NF-κB) in LoVo cells was evaluated by immunoblotting and luciferase assay, and the invasion ability of LoVo cells after different treatments was determined using cell invasion assay. In vivo, xenograft tumor model was established and the correlation of TCTP and HMGB1 expression in xenografted tumors was studied by immunohistochemical examination. The results revealed that the expression level of TCTP in CRC tissue and the serum concentration of HMGB1 in patients with CRC were significantly increased, and there was a strong positive correlation between them. In vitro experiments showed that the overexpression of TCTP on LoVo cells resulted in the release of HMGB1 from the nucleus to the cytoplasm and into the extracellular space. In addition, the overexpression of TCTP led to the activation of NF-κB in LoVo cells, and this effect was reversed by treatment with antibodies targeting HMGB1 or to its receptors Toll-like receptor 4 (TLR4) and receptor for advanced glycation end products advanced glycation end products (RAGE). Furthermore, inhibition of the HMGB1-TLR4/RAGE-NF-κB pathway significantly inhibited the TCTP-stimulated invasion of LoVo cells. In vivo experiments demonstrated that the overexpression of TCTP in nude mice promoted the development and spread of xenografted tumors, and concurrently enhanced the expression of HMGB1 in tumor tissues. Collectively, these findings suggested that TCTP promotes CRC metastasis through regulating the behaviors of HMGB1 and the downstream activation of the NF-κB signaling pathway.

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