HLTF suppresses the migration and invasion of colorectal cancer cells via TGF‑β/SMAD signaling in vitro

Liu,Li; Liu,Huan; Zhou,Yangying; He,Jiaofeng; Liu,Qiong; Wang,Jian; Zeng,Manting; Yuan,Dan; Tan,Fengbo; Zhou,Yuan; Pei,Haiping; Zhu,Hong

doi:10.3892/ijo.2018.4591

HLTF suppresses the migration and invasion of colorectal cancer cells via TGF‑β/SMAD signaling in vitro

Authors:
- Li Liu
- Huan Liu
- Yangying Zhou
- Jiaofeng He
- Qiong Liu
- Jian Wang
- Manting Zeng
- Dan Yuan
- Fengbo Tan
- Yuan Zhou
- Haiping Pei
- Hong Zhu
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Affiliations: Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China, Department of Oncology, Hunan Academy of Traditional Chinese Medicine Affiliated Hospital, Changsha, Hunan 410008, P.R. China, Department of Oncology, Zhuzhou No. 2 Hospital, Zhuzhou, Hunan 412005, P.R. China, Department of Gastrointestinal Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Published online on: October 10, 2018 https://doi.org/10.3892/ijo.2018.4591
Pages: 2780-2788

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Abstract

Helicase‑like transcription factor (HLTF) has been identified as a tumor suppressor gene. The hypermethylation of HTLF is frequently observed in various types of cancer, including colorectal cancer (CRC). However, the mechanisms through which HLTF suppresses CRC progression remain unclear. Thus, the aim of the present study was to explore the biological function of HLTF in CRC cells and the underlying mechanisms. CRC tissues and cells were used to detect the expression of HLTF. Wound‑healing and Transwell assays were performed to assess the motility of CRC cells. The results revealed that HLTF expression was significantly associated with the differentiation status, invasion depth, lymph node metastasis and distant metastasis. A low HLTF expression was significantly associated with a poor survival. Furthermore, HTLF knockdown or ectopic overexpression significantly promoted or suppressed the motility of CRC cells, respectively. With regard to the underlying molecular mechanisms, the protein expression of HTLF was upregulated when the CRC cells were stimulated with transforming growth factor (TGF)‑β, and HLTF upregulation induced an increase in SMAD4 and p‑SMAD2/3 expression and a decrease in levels of the TGF‑β/SMAD pathway downstream genes, Vimentin and zinc finger e‑box binding homeobox 1 (ZEB1). On the whole, the findings of this study suggest that HLTF is negatively associated with the progression of CRC, and its overexpression suppresses the migration and invasion of CRC cells by targeting the TGF‑β/SMAD pathway.

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