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Updated: Sep 19, 2025
08:45
Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
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Shp2 regulates the trophoblast cell cycle progression through p53-p21 pathway modulation.
Ming-Hui Meng1, Xin Wu1, Ting Qin1
1Medical Genetics and Prenatal Diagnosis Center, Guangxi Academy of Medical Sciences and the People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530021, China.
Biochemical and Biophysical Research Communications
|June 17, 2025
Summary
Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp2) inactivation inhibits trophoblast cell proliferation and migration. Shp2 likely maintains cell cycle progression by suppressing the p53-p21 axis, impacting placental development.
Area of Science:
- Reproductive biology
- Molecular and cellular biology
- Biochemistry
Background:
- Trophoblast cell proliferation and migration are vital for placental development.
- Dysfunctional trophoblast cells are linked to pregnancy complications like preeclampsia and fetal growth restriction.
Purpose of the Study:
- To investigate the role of Src homology 2 domain-containing protein tyrosine phosphatase 2 (Shp2) in regulating trophoblast cell functions.
- To elucidate the molecular mechanisms by which Shp2 influences trophoblast behavior.
Main Methods:
- Utilized a specific Shp2 inhibitor (SHP099) and lentivirus-mediated Shp2 knockdown.
- Employed transcriptome sequencing to analyze gene expression changes.
- Confirmed protein level alterations via Western blot analysis.
Main Results:
- Shp2 inactivation significantly inhibited trophoblast cell (HTR8) proliferation and induced G0/G1 cell cycle arrest.
- Reduced migratory and invasive capacities of trophoblast cells were observed upon Shp2 inhibition.
- Shp2 knockdown upregulated p53 pathway genes (e.g., CDKN1A, MDM2) and increased p21 protein levels.
- Shp2 modulated Erk1/2 and Akt signaling pathways, indicating involvement in MAPK and PI3K-Akt signaling.
Conclusions:
- Shp2 plays a critical role in maintaining trophoblast cell proliferation and migration.
- Shp2 likely suppresses the p53-p21 axis to promote cell cycle progression.
- Shp2 influences trophoblast functions via MAPK and PI3K-Akt signaling pathways.
- Shp2 represents a potential therapeutic target for placental disorders.
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