PTPRZ1 regulates calmodulin phosphorylation and tumor progression in small-cell lung carcinoma

Hideki Makinoshima1, Genichiro Ishii, Motohiro Kojima

  • 1Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.

BMC Cancer
|November 23, 2012
PubMed
Abstract

Insights

Protein tyrosine phosphatase receptor Z1 (PTPRZ1) is highly expressed in small-cell lung carcinoma (SCLC) and promotes tumor progression. Targeting the PTN/PTPRZ1 pathway may offer new treatment strategies for neuroendocrine tumors (NETs).

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype with poor prognosis and limited treatment options.
  • There is a critical need for novel targeted molecular agents for SCLC treatment.

Purpose of the Study:

  • To investigate the role of PTPRZ1 in SCLC and neuroendocrine tumors (NETs).
  • To explore the potential of the PTN/PTPRZ1 signaling pathway as a therapeutic target.

Main Methods:

  • RT-PCR screening of 20 cell lines.
  • Immunohistochemical examination of 252 primary tumors for PTPRZ1 expression.
  • shRNA-mediated PTPRZ1 down-regulation to assess effects on tyrosine phosphorylation and tumor progression in SCLC models.

Main Results:

  • PTPRZ1 is highly expressed in SCLC cell lines and human NET tissues.
  • The PTN/PTPRZ1 pathway activation induces tyrosine phosphorylation of calmodulin (CaM) in SCLC cells.
  • PTPRZ1 plays a significant oncogenic role in SCLC tumor progression, as evidenced by murine xenograft models.

Conclusions:

  • PTPRZ1 is an oncogenic tyrosine phosphatase highly expressed in human NET tissues and SCLCs.
  • The PTN/PTPRZ1 signaling pathway represents a potential therapeutic target for NETs.

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