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Updated: Mar 30, 2026

Assessing Cellular Target Engagement by SHP2 PTPN11 Phosphatase Inhibitors
Published on: July 17, 2020
A PTEN translational isoform has PTEN-like activity
Xie Zhang1, Bowei Yin1, Fangfang Zhu1
11 Department of Gastroenterology, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang, China ; 2 School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China ; 3 Ningbo Medical Center, 4 Minimally Invasive Abdominal Surgery, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang Province, China.
A newly identified PTEN isoform, larger than the standard PTEN protein, demonstrates tumor suppressor functions by inhibiting cell growth and promoting apoptosis. This PTEN isoform may represent a novel target for cancer therapy.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- The phosphatase and tensin homolog (PTEN) is a critical tumor suppressor.
- The existence and function of a PTEN isoform were previously unknown.
Purpose of the Study:
- To identify and characterize a novel PTEN isoform.
- To investigate the role of this PTEN isoform in tumor suppression and the PI3K-Akt signaling pathway.
Main Methods:
- Western blotting, immunoprecipitation, and bioinformatic analysis were employed to identify and validate the PTEN isoform.
- Cellular assays including proliferation, apoptosis, and migration assays were performed to assess biological activities.
- Overexpression and shRNA-mediated knockdown techniques were utilized to study PTEN isoform expression and function.
Main Results:
- A PTEN isoform approximately 15 kDa larger than PTEN was identified, with expression dependent on PTEN status.
- The PTEN isoform is not a result of common post-translational modifications; its expression originates from an alternative upstream CTG start codon.
- Overexpression of the PTEN isoform suppressed the PI3K-Akt pathway, reduced cell growth, enhanced apoptosis, and inhibited cell migration.
Conclusions:
- The identified PTEN isoform possesses PTEN-like tumor suppressor activity.
- This PTEN isoform represents a potential new player in tumor suppression and warrants further investigation.
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