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Updated: May 16, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
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.
Background:
Small-cell lung carcinoma (SCLC) is a neuroendocrine tumor subtype and comprises approximately 15% of lung cancers. Because SCLC is still a disease with a poor prognosis and limited treatment options, there is an urgent need to develop targeted molecular agents for this disease.
Methods:
We screened 20 cell lines from a variety of pathological phenotypes established from different organs by RT-PCR. Paraffin-embedded tissue from 252 primary tumors was examined for PTPRZ1 expression using immunohistochemistry. shRNA mediated PTPRZ1 down-regulation was used to study impact on tyrosine phosphorylation and in vivo tumor progression in SCLC cell lines.
Results:
Here we show that PTPRZ1, a member of the protein tyrosine- phosphatase receptor (PTPR) family, is highly expressed in SCLC cell lines and specifically exists in human neuroendocrine tumor (NET) tissues. We also demonstrate that binding of the ligand of PTPRZ1, pleiotrophin (PTN), activates the PTN/PTPRZ1 signaling pathway to induce tyrosine phosphorylation of calmodulin (CaM) in SCLC cells, suggesting that PTPRZ1 is a regulator of tyrosine phosphorylation in SCLC cells. Furthermore, we found that PTPRZ1 actually has an important oncogenic role in tumor progression in the murine xenograft model.
Conclusion:
PTPRZ1 was highly expressed in human NET tissues and PTPRZ1 is an oncogenic tyrosine phosphatase in SCLCs. These results imply that a new signaling pathway involving PTPRZ1 could be a feasible target for treatment of NETs.
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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