Research Papers:

This article has been retracted. Retraction in: Oncotarget. 2018; 9:23845.

PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation

Qiang Ma, Xiuxiu Wu, Jing Wu, Huanwen Wu, Ying Xiao, Lili Wang, Zhiyong Liang _ and Tonghua Li

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Oncotarget. 2017; 8:72893-72909. https://doi.org/10.18632/oncotarget.20552

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Qiang Ma1,*, Xiuxiu Wu2,*, Jing Wu3, Huanwen Wu1, Ying Xiao1, Lili Wang1, Zhiyong Liang1 and Tonghua Liu1

1Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China

2Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, P. R. China

3Department of Medical Imaging, Beijing Huairou Hospital, University of Chinese Academy of Science, Beijing, 101400, P.R. China

*Authors contributed equally to this work

Correspondence to:

Zhiyong Liang, email: [email protected]

Tonghua Liu, email: [email protected]

Keywords: pancreatic cancer, prognosis, PDZK1, PTEN phosphorylation, suppressor

Received: July 11, 2017     Accepted: July 31, 2017     Published: August 24, 2017


Phosphorylation is a recently established cause of phosphatase and tensin homolog (PTEN) gene inactivation, which leads to defect tumour-suppressor function. In pancreatic cancer, this phenomenon has not been reported. Based on database and clinical sample analyses, we found that PTEN phosphorylation occurs in pancreatic ductal adenocarcinoma patient tissues and cell lines, and we aimed to find a method for dephosphorylation. PDZ-containing 1 (PDZK1), a tumour-associated protein that shares its PDZ-binding sequence with the carboxyl-terminal domain of PTEN, was significantly down-regulated in pancreatic cancer as compared to adjacent non-tumour tissues. In vitro, PDZK1 overexpression reversed the proliferation and migration abilities of pancreatic cancer cells and led to significantly decreased PTEN phosphorylation and AKT phosphorylation by interacting with wild-type PTEN. In addition, a transcription factor-activation assay supported that PDZK1 overexpression enhanced the anti-oncogene function of PTEN by regulating the activities of its downstream transcription factors, including p53, NF-κB, and FOXO1. In vivo, nude mice stably over-expressing PDZK1 had lower tumour weights and volumes and showed significantly down-regulated PTEN phosphorylation in xenograft tumour tissues as compared to the control group. Moreover, low PDZK1 expression strongly correlated with advanced stage and poor prognosis of patients with pancreatic ductal adenocarcinoma. In conclusion, our study elucidated the tumour-suppressor role of PDZK1 in pancreatic cancer through down-regulating PTEN phosphorylation, and established PDZK1 as a potential novel prognostic marker for pancreatic cancer.

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