The hotspot mutation H1047R in the oncogenic PIK3CA gene is frequently detected in breast cancer and enhances the enzymatic activity of PI3K to activate AKT/mTOR signaling cascade. Aberrant elevated PI3K activation has been reported to promote the tumorigenesis of breast cancer.

Research group led by MENG Linghua and DING Jian from the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences recently revealed the previously unappreciated role of activating PIK3CAH1047R in breast cancer, which has been published in International Journal of Cancer.

The research group has been devoted in studying the role of PI3K in tumorigenesis and the therapeutic potential of PI3K as an anti-cancer target. By establishing human mammary epithelial MCF-10A cells stably expressing PIK3CAH1047R, they found that PIK3CAH1047R induced cellular senescence accompanied with enhanced secretion of pro-tumorigenic factors.

Similar results were obtained in breast cancer cells harboring H1047R mutation. Interestingly，membrane metallo-endopeptidase was found to mediate PI3Kα-induced senescence and contributed to the pro-tumorigenic senescence-associated secretome.

“Mutations in PIK3CA occur in approximately 40% of breast cancer cases and PI3Ka has been validated as a promising target for the therapy for the breast cancer.” Said Prof. MENG Linghua.

Their study sheds new insight on the mechanisms of PI3K-promoted tumorigenesis and provides new clues for the intervention of tumors with activated PI3K signaling.

This work was supported by "Personalized Medicines-Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences, National Science and Technology Major Project “Key New Drug Creation and Manufacturing Program and National Natural Science Foundation of China.

Full text link: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ijc.32153