SHCBP1 is a novel regulator of PLK1 phosphorylation and promotes prostate cancer bone metastasis

Abstract Prostate cancer is a common male genitourinary malignancy with bone metastasis posing challenges for prognosis and treatment. This study aimed to investigate the role of SHC protein SH2 structural domain binding protein 1 (SHCBP1) in prostate cancer bone metastasis. Whole transcriptome sequencing of prostate cancer samples was conducted to identify oncogene expression, specifically focusing on SHCBP1. In vivo and in vitro models were used to study SHCBP1's impact on bone metastasis. Through co‐immunoprecipitation, mass spectrometry, and Western blot assays, the interaction between SHCBP1 and cell cycle‐related proteins was elucidated, along with analysis of downstream protein partners. SHCBP1 was found to enhance prostate cancer cell development, metastasis, and mitosis, with the SHCBP1—polo‐like kinase 1 (PLK1)—CDC25C axis playing a key role in promoting tumorigenesis. Therapeutic inhibition of SHCBP1 increased docetaxel sensitivity. Clinical data showed elevated SHCBP1 expression in advanced prostate cancer stages. These findings offer insights into potential therapeutic strategies for prostate cancer bone metastasis and highlight the significance of the SHCBP1‐PLK1‐CDC25C axis in docetaxel sensitivity.