
The dysregulated PI3K/AKT pathway plays a key role in prostate cancer progression but poses therapeutic challenges due to compensatory pathway upregulation. This study uncovers the novel regulatory function of RACK1, an adaptor protein, in modulating AKT activation and driving prostate cancer development. Using a genetic mouse model, researchers found that RACK1 is essential for AKT membrane translocation and its interaction with mTORC2, leading to tumor formation. Importantly, RACK1 deficiency blocked AKT activation and prevented tumor growth without feedback upregulation of HER3 or androgen receptor (AR) pathways, unlike direct PI3K/AKT inhibition. These findings suggest RACK1 as a potential therapeutic target for managing PI3K/AKT-driven prostate cancer.
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