TGF(3-activated Asporin interacts with STMN1 to promote prostate cancer docetaxel chemoresistance and metastasis by upregulating the Wnt/ (3-catenin signaling pathway

Aims: Prostate cancer (PCa) remains a significant challenge in oncology due to high rates of drug resistance following standard treatment with docetaxel-based chemotherapy. Asporin (ASPN) has been regarded as an oncogene and its upregulation is closely associated with malignant behavior and poor prognosis in multiple cancers. Studies indicated that abnormal activation of the Wnt/(3-catenin signaling pathway is prevalent in PCa. This study investigated the important role of ASPN in regulating Wnt/(3-catenin signaling pathway in docetaxel resistance and metastasis of PCa. Methods: The impacts of ASPN on the docetaxel chemoresistance and metastasis of PCa cells were investigated in vitro and in vivo assays. Lastly, the underlying mechanism of ASPN was revealed by Western blot, protein immunocoprecipitation, Immunofluorescence, Immunohistochemical staining, liquid chromatography-mass spectrometry, and rescue experiments. Results: In present study, we reported that ASPN is highly expressed in PCa cells and tissues. Functional and molecular analyses showed that ASPN is activated by TGF(3 and interacts with STMN1. ASPN increases the expression of (3-catenin and promotes its nuclear accumulation by mediating the activation of the Wnt/(3-catenin signaling pathway, thereby enhancing the stemness and epithelial-mesenchymal transition (EMT) of PCa cells, ultimately facilitating the docetaxel resistance and metastasis of PCa cells. Conclusions: Our findings identify ASPN as a novel upstream regulatory factor of Wnt/(3-catenin signaling pathway, suggesting that targeting the ASPN/STMN1/(3-catenin axis could be a promising strategy for PCa intervention.