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Updated: Mar 29, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
Expression and clinical significance of tyrosine phosphatase SHP2 in thyroid carcinoma
Zhong-Qian Hu1, Rui Ma2, Chi-Min Zhang1
1Department of Ultrasound, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Abstract:
Protein-tyrosine phosphatase SHP2 is encoded by the gene PTPN11. SHP2 is hypothesized to have a critical role in cancer, via the activation of mutations that have been detected in several types of leukaemia and in certain solid tumours, including liver, breast, gastric and cervical cancer. However, to the best of our knowledge, there have been no previous reports evaluating the significance of SHP2 expression in thyroid cancer. The present study evaluated SHP2 expression in 65 thyroid cancer specimens, 40 specimens of self-matched adjacent peritumour tissues and 40 specimens of normal thyroid tissue, using immunohistochemical and western blot analyses with an anti-SHP2 antibody. Western blotting was also used to assess SHP2 expression in thyroid cancer cell lines (SW579, IHH-4, FTC-133, TPC-1, DRO, TA-K, and ML-1) and Nthy-ori3-1 normal thyroid cells. In addition, SHP2 antisense oligonucleotides were used to block SHP2 expression in SW579 cells, and growth inhibition assays were conducted. Increased SHP2 expression was detected in the tumour tissues compared with that of the normal thyroid tissues (P<0.05). SHP2 expression was significantly correlated with poor tumour differentiation (P<0.05), late TNM stage (P<0.05) and lymph node metastasis (P<0.05), suggesting that SHP2 may represent a potential target for thyroid cancer therapy.
Insights
This study investigated the role of Protein-tyrosine phosphatase SHP2 in thyroid cancer. Increased SHP2 expression was found in thyroid tumors and correlated with advanced disease, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Protein-tyrosine phosphatase SHP2, encoded by PTPN11, is implicated in various cancers.
- SHP2 mutations are found in leukemia and solid tumors like liver, breast, gastric, and cervical cancers.
- The significance of SHP2 expression in thyroid cancer remains largely unexplored.
Purpose of the Study:
- To evaluate SHP2 expression levels in thyroid cancer tissues.
- To determine the correlation between SHP2 expression and clinicopathological features of thyroid cancer.
- To investigate the potential of SHP2 as a therapeutic target in thyroid cancer.
Main Methods:
- Immunohistochemical and Western blot analyses were used to assess SHP2 expression in 65 thyroid cancer specimens, adjacent peritumour tissues, and normal thyroid tissues.
- SHP2 expression was also analyzed in various thyroid cancer cell lines and normal thyroid cells.
- SHP2 function was investigated in SW579 cells using antisense oligonucleotides and growth inhibition assays.
Main Results:
- Significantly increased SHP2 expression was observed in thyroid tumour tissues compared to normal thyroid tissues (P<0.05).
- Elevated SHP2 expression correlated with poor tumour differentiation (P<0.05), advanced TNM stage (P<0.05), and lymph node metastasis (P<0.05).
- Blocking SHP2 expression in SW579 cells led to growth inhibition.
Conclusions:
- SHP2 is overexpressed in thyroid cancer.
- SHP2 expression is associated with aggressive clinicopathological features in thyroid cancer.
- SHP2 represents a promising therapeutic target for thyroid cancer treatment.
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