OncoTargets and Therapy (Oct 2019)
PTPRU, As A Tumor Suppressor, Inhibits Cancer Stemness By Attenuating Hippo/YAP Signaling Pathway
Abstract
Jiayi Gu,1,* Zhiqi Zhang,2,* Tingyuan Lang,3,* Xinlin Ma,1 Linxi Yang,1 Jia Xu,1 Cong Tian,4 Kun Han,4 Jiangfeng Qiu1 1Department of Gastrointestinal Surgery, Renji Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200127, People’s Republic of China; 2Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China; 3Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing 400030, People’s Republic of China; 4Department of Medical Oncology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiangfeng QiuDepartment of Gastrointestinal Surgery, Renji Hospital Shanghai Jiao Tong University School of Medicine, No.160 Pujian Road, Pudong New Area, Shanghai 200127, People’s Republic of ChinaTel +86 138 1687 3899Fax +86 21 6373 0455Email [email protected]: PTPRU is an important signaling molecule that regulates a variety of cellular processes; however, the role of PTPRU in cancer development has remained elusive. Here, we report that PTPRU serves as a tumor suppressor that inhibits cancer stemness by attenuating Hippo/YAP signaling pathway.Methods: Primary cancer cells and cell line cells were used in the study. The gene expression data were downloaded from R2 analysis and visualization platform and Kaplan–Meier analysis was performed to study the relationship between survival and PTPRU expression. qRT-PCR and Western blot were employed to study the expression of target genes in tissues and cells. Sphere and colony formation, proliferation, migration activities and the expression of stem cell and EMT markers were employed for characterizing the stemness. Gene manipulation was achieved by lentivirus-mediated gene delivery system. Luciferase reporter gene assay was used to study the transcriptional activity of the promoter, and ChIP-qPCR was employed to study the target binding sequence of the protein. Spearman correlation analysis was performed to study the correlation between two genes. Student’s t-test was used for determination of the significance between two experimental groups.Results: PTPRU is downregulated in colorectal and gastric cancer tissues and cancer stem cells. High expression of PTPRU predicts poor prognosis. Overexpression of PTPRU attenuates the stemness of gastric cancer stem cells and knockdown of PTRPU improves the maintenance of the stemness of cancer stem cells. Mechanistic analysis showed that PTPRU inhibits Hippo/YAP signaling by suppressing the expression of YAP in a transcriptional level. Overexpression of YAP restored PTPRU-induced inhibited stemness of gastric cancer stem cells.Conclusion: PTPRU serves as a tumor suppressor that inhibits the stemness of cancer stem cell by inhibiting Hippo/YAP signaling pathway.Keywords: PTPRU, cancer stem cells, Hippo/YAP signaling, gastric cancer, colorectal cancer
