THBS2 Promotes Prostate Cancer Malignancy via INHBA-Dependent FAK/PI3K/AKT Signaling Activation

Prostate cancer (PCa) is a leading malignancy among men, with a growing incidence and mortality rate worldwide. There is a pressing need to identify novel molecular biomarkers and therapeutic targets to improve prognosis and treatment strategies for PCa. We analyzed thrombospondin 2 (THBS2) expression patterns in PCa using The Cancer Genome Atlas (TCGA) datasets and validated findings in clinical tissues and cell lines. Functional assays, including Cell Counting Kit (CCK)-8 proliferation, flow cytometry apoptosis, wound healing, and Transwell invasion, were performed on PCa cell lines with altered THBS2 expression. Bioinformatic analyses were conducted to explore THBS2-related pathways, and protein interactions were examined via STRING and Western blot. THBS2 expression was significantly upregulated in PCa tissues and cell lines and correlated with advanced clinicopathological features and poor prognosis. Overexpression of THBS2 promoted PCa cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while inhibiting apoptosis. Mechanistically, THBS2 interacted with INHBA to activate the focal adhesion kinase (FAK)/PI3K/AKT signaling pathway, facilitating malignant progression. INHBA knockdown reversed the oncogenic effects of THBS2, indicating a synergistic interaction between THBS2 and INHBA in PCa pathogenesis. THBS2 acts as an oncogene in PCa by promoting proliferation, invasion, and EMT via the FAK/PI3K/AKT pathway in cooperation with INHBA. These findings highlight THBS2 as a promising biomarker for PCa.