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Updated: Jul 19, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation
Jean J Zhao1, Hailing Cheng, Shidong Jia
1Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA. jean_zhao@dfci.harvard.edu
Abstract:
Growth factor signaling is mediated through Class IA phosphatidylinositol 3-kinases (PI3Ks). Among this class of enzymes, only p110alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers. To determine the specific functions of p110alpha, we generated mice carrying a conditionally targeted allele of the PIK3CA gene. Here, we report that PIK3CA-knockout mouse embryonic fibroblasts are deficient in cellular signaling in response to various growth factors, unable to differentiate into adipocytes, and resistant to oncogenic transformation induced by a variety of oncogenic receptor tyrosine kinases, indicating a fundamental role for p110alpha in these biological processes.
Insights
The PIK3CA gene
Area of Science:
- Molecular Biology
- Cellular Signaling
- Cancer Research
Background:
- Growth factor signaling relies on Class IA phosphatidylinositol 3-kinases (PI3Ks).
- The PIK3CA gene, encoding p110alpha, is frequently mutated in human cancers.
Purpose of the Study:
- To investigate the specific biological functions of p110alpha.
- To understand the role of PIK3CA in cellular processes and oncogenesis.
Main Methods:
- Generation of mice with a conditionally targeted PIK3CA allele.
- Analysis of PIK3CA-knockout mouse embryonic fibroblasts (MEFs).
Main Results:
- PIK3CA-knockout MEFs exhibited impaired growth factor signaling.
- These cells were unable to undergo adipocyte differentiation.
- Resistance to oncogenic transformation by receptor tyrosine kinases was observed.
Conclusions:
- p110alpha plays a critical role in growth factor-mediated signaling.
- PIK3CA is essential for adipocyte differentiation and cellular transformation.
- These findings highlight p110alpha as a key mediator in fundamental biological processes and cancer development.
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