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Development and Application of Rapamycin-regulated Tyrosine Phosphatases
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Development and Application of Rapamycin-regulated Tyrosine Phosphatases

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Identification and functional characterization of paxillin as a target of protein tyrosine phosphatase receptor T

Yiqing Zhao1, Xiaodong Zhang, Kishore Guda

  • 1College of Life Sciences, Sichuan University, Chengdu 610064, China.

Proceedings of the National Academy of Sciences of the United States of America
|February 6, 2010
PubMed

Insights

Protein tyrosine phosphatase receptor-type T (PTPRT) suppresses colorectal cancer by regulating paxillin phosphorylation. Loss of PTPRT function increases paxillin phosphorylation, promoting tumor growth and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Protein tyrosine phosphatase receptor-type T (PTPRT) is frequently mutated in human cancers, but its regulatory pathways are unclear.
  • Understanding PTPRT's role is crucial for developing targeted cancer therapies.

Purpose of the Study:

  • To elucidate the cell signaling pathways regulated by PTPRT.
  • To investigate the role of PTPRT in colorectal cancer (CRC) tumorigenesis.

Main Methods:

  • Investigated PTPRT-paxillin interaction and PTPRT's regulation of paxillin phosphorylation at Y88 in CRC cells.
  • Utilized paxillin Y88F knock-in CRC cells and PTPRT knockout mice.
  • Assessed cell migration, anchorage-independent growth, xenograft tumor formation, and phosphorylation of downstream targets (p130CAS, SHP2, AKT).

Main Results:

  • PTPRT directly phosphorylates paxillin at Y88 in CRC cells.
  • Paxillin Y88F mutation significantly reduced cell migration, anchorage-independent growth, and xenograft tumor formation.
  • PTPRT knockout mice showed increased colonic paxillin phosphorylation and heightened susceptibility to azoxymethane-induced colon tumors.
  • Elevated paxillin pY88 is a common feature in human colon cancers.

Conclusions:

  • PTPRT acts as a tumor suppressor in colorectal cancer by regulating paxillin phosphorylation at Y88.
  • This PTPRT-paxillin signaling pathway is critical in colorectal tumorigenesis.
  • Findings identify PTPRT as a potential therapeutic target for colon cancer.

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