PTEN Loss Promotes PI3Kβ Phosphorylation and EPHA2/SRC/p-PI3KβY962 Complex Assembly to Drive Tumorigenesis
We revealed a critical new mechanism that PTEN loss induces PI3Kβ phosphorylation and EPHA2/SRC/p-PI3KβY962 complex signaling to drive tumorigenesis. This work directs pharmaceutical development of p-PI3KβY962 inhibitors and biomarker-driven clinical trials repurposing dasatinib for PTEN-deficient solid tumor treatment, with potential to significantly improve outcomes of broad patients with PTEN-deficient tumors.
Authors
- Yutong Li (ORCID: https://orcid.org/0009-0002-1468-4151)
- Shuang Tang (ORCID: https://orcid.org/0000-0002-3501-7836)
- Da‐Qiang Li (ORCID: https://orcid.org/0000-0002-5113-2332)
- Tao Jiang
- X. Steven Wan (ORCID: https://orcid.org/0000-0002-3801-6409)
- Thomas M. Roberts (ORCID: https://orcid.org/0000-0001-6453-3955)
- Jean J. Zhao (ORCID: https://orcid.org/0000-0002-4561-5688)
- Renlei Ji (ORCID: https://orcid.org/0000-0001-6258-1777)
- Jared L. Johnson (ORCID: https://orcid.org/0000-0003-1802-6527)
- Lewis C. Cantley (ORCID: https://orcid.org/0000-0002-1298-7653)
- Tomer M. Yaron (ORCID: https://orcid.org/0000-0001-6574-7314)
- Johann S. Bergholz (ORCID: https://orcid.org/0000-0003-4609-8448)
- Bo Dai (ORCID: https://orcid.org/0000-0001-9827-3581)
- Xiaoling Li (ORCID: https://orcid.org/0000-0001-5920-7784)
- Zefeng Wang (ORCID: https://orcid.org/0000-0002-6605-3637)
- Xiadi He (ORCID: https://orcid.org/0009-0001-8171-9505)
- Wendi Huang (ORCID: https://orcid.org/0000-0003-3571-9288)
- Jiachen Wu (ORCID: https://orcid.org/0009-0003-6089-2733)
- Qian Zhou (ORCID: https://orcid.org/0000-0003-1471-6651)
- Meng-Hong Sun (ORCID: https://orcid.org/0009-0001-7120-5535)
- Qianchen Jing (ORCID: https://orcid.org/0009-0005-9003-4339)
- Weihua Wang
Institutions
- Shanghai Medical College of Fudan University (CN)
- Harvard University (US)
- Cornell University (US)
- Fudan University (CN)
- Inner Mongolia University (CN)
- Southern University of Science and Technology (CN)
- Lander Institute (IL)
- Triangle (US)
- Fudan University Shanghai Cancer Center (CN)
- National Institute of Environmental Health Sciences (US)
- Shanghai Institute of Nutrition and Health (CN)
- Dana-Farber Cancer Institute (US)
- Center for Excellence in Molecular Cell Science (CN)
- Harvard Stem Cell Institute (US)
- Columbia University (US)
Publication Details
- Journal
- Cancer Discovery
- Published
- 2025-11-14
- DOI
- https://doi.org/10.1158/2159-8290.cd-25-1126
- Citations
- 1
- Primary Topic
- PI3K/AKT/mTOR signaling in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.81