SP1 reduces autophagic flux through activating p62 in gastric cancer cells

Xu,Xiao‑Wu; Pan,Chen‑Wei; Yang,Xiao‑Min; Zhou,Lei; Zheng,Zhi‑Qiang; Li,De‑Chun

doi:10.3892/mmr.2018.8400

SP1 reduces autophagic flux through activating p62 in gastric cancer cells

Authors:
- Xiao‑Wu Xu
- Chen‑Wei Pan
- Xiao‑Min Yang
- Lei Zhou
- Zhi‑Qiang Zheng
- De‑Chun Li
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Affiliations: Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China, Department of Infectious Diseases, The Second Affiliated Hospital and Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China, Department of Pathology, Wenzhou People's Hospital, Wenzhou, Zhejiang 325027, P.R. China, Department of General Surgery, The Second Affiliated Hospital and Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China
Published online on: January 9, 2018 https://doi.org/10.3892/mmr.2018.8400
Pages: 4633-4638

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Abstract

Gastric cancer is the most common type of gastrointestinal cancer, causing mortality worldwide. However, the underlying molecular mechanism in gastric cancer progression remains unclear. The autophagic flux was determined in gastric cancer cells overexpressing or inhibiting Sp1 transcription factor (SP1) using western blotting, reverse transcription‑polymerase chain reaction and immunofluorescence staining. Luciferase and ChIP assays were performed to detect the potential underlying mechanism of SP1 in gastric cancer cells. Lastly, immunohistochemistry was also performed on SP1 and p62 expression levels in human gastric cancer specimens. It was demonstrated that SP1 diminished autophagic flux via activating p62 in gastric cancer. Moreover, SP1 deficiency increased the rate of autophagy of gastric cancer cells. Notably, it was observed that SP1 enhanced the expression levels of p62 by directly binding to the promoter of p62. Analysis of gastric cancer specimen staining established that p62 expression levels were increased in SP1‑positve gastric tissues. The present study provided evidence for a novel mechanism regulating autophagy in gastric cancer cells.

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