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PTPRU, As A Tumor Suppressor, Inhibits Cancer Stemness By Attenuating Hippo/YAP Signaling Pathway

Jiayi Gu1, Zhiqi Zhang2, Tingyuan Lang3

  • 1Department of Gastrointestinal Surgery, Renji Hospital Shanghai Jiao Tong University School of Medicine, Shanghai 200127, People's Republic of China.

Oncotargets and Therapy
|October 22, 2019
PubMed
Abstract

Insights

Protein tyrosine phosphatase, receptor type U (PTPRU) acts as a tumor suppressor by inhibiting cancer stemness. PTPRU attenuates the Hippo/YAP signaling pathway, impacting cancer development and prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Protein tyrosine phosphatase, receptor type U (PTPRU) is a key signaling molecule with largely unknown roles in cancer.
  • This study investigates the function of PTPRU in cancer development and its association with cancer stemness.

Purpose of the Study:

  • To elucidate the role of PTPRU in cancer, specifically its impact on cancer stemness.
  • To determine the molecular mechanisms by which PTPRU regulates cancer stemness, focusing on the Hippo/YAP signaling pathway.

Main Methods:

  • Analysis of PTPRU expression in colorectal and gastric cancer tissues and cell lines.
  • Functional assays including sphere formation, proliferation, and migration to assess cancer stemness.
  • Gene manipulation using lentivirus systems and molecular analyses (qRT-PCR, Western blot, luciferase reporter assays, ChIP-qPCR).
  • Statistical analyses including Kaplan-Meier and Spearman correlation.

Main Results:

  • PTPRU is downregulated in colorectal and gastric cancers and is associated with poor prognosis.
  • Overexpression of PTPRU reduces cancer stemness, while its knockdown enhances it.
  • PTPRU suppresses the Hippo/YAP signaling pathway by reducing YAP expression transcriptionally.
  • Restoration of YAP expression reverses the inhibitory effect of PTPRU on cancer stemness.

Conclusions:

  • PTPRU functions as a tumor suppressor by inhibiting cancer stemness.
  • The tumor-suppressive activity of PTPRU is mediated through the attenuation of the Hippo/YAP signaling pathway.
Keywords:
Hippo/YAP signalingPTPRUcancer stem cellscolorectal cancergastric cancer

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