Huang Wei-Lun, Chen Sih-Han, Wu Richard Chen-Yu, Mai Hsing-Cha, Wu Chun-Hsien, Hsieh Pei-Fang, Pang See-Tong, Lin Victor Chia-Hsiang
Division of Urology, Department of Surgery, E-Da Hospital Kaohsiung 824, Taiwan.
Department of Nursing, I-Shou University Kaohsiung 840, Taiwan.
Am J Cancer Res. 2024 Oct 15;14(10):4717-4730. doi: 10.62347/YQWJ7498. eCollection 2024.
Androgen deprivation therapies, the key treatment options for prostate cancer, have shown resistance and disease progression in many patients receiving these treatments. Therefore, it is crucial to identify new targetable pathways. Epidermal growth factor receptor pathway substrate 8 (Eps8) is one such potential target. Although this pathway is associated with the progression of various cancers, studies on the role of Eps8 in prostate cancer remain limited. This study investigated the role of Eps8 in prostate cancer. The LNCaP cell line and enzalutamide-resistant LNCaP (LNCaP Enz-R) cell lines were utilized for the investigation. Overexpression of Eps8 was observed in the LNCaP Enz-R cells. Transfecting pCMV-EPS8 also increased the levels of epithelial-to-mesenchymal transition (EMT), cell proliferation, and cell viability in both cell lines. Conversely, knockdown of Eps8 expression decreased the levels of EMT, cell proliferation, and cell viability in both cell lines. Furthermore, EPS8-induced EMT activation could be reversed by suppressing the Ras/JAK/PI3K signaling pathway. In vivo animal study also confirmed the crucial role of Eps8 expression in prostate cancer progression. Therefore, we suggest that targeting Eps8 by knocking down its expression is promising as a therapeutic approach for prostate cancer treatment.
雄激素剥夺疗法是前列腺癌的关键治疗选择，但在许多接受这些治疗的患者中已显示出耐药性和疾病进展。因此，确定新的可靶向通路至关重要。表皮生长因子受体通路底物8（Eps8）就是这样一个潜在靶点。尽管该通路与多种癌症的进展相关，但关于Eps8在前列腺癌中作用的研究仍然有限。本研究调查了Eps8在前列腺癌中的作用。使用LNCaP细胞系和恩杂鲁胺耐药的LNCaP（LNCaP Enz-R）细胞系进行研究。在LNCaP Enz-R细胞中观察到Eps8的过表达。转染pCMV-EPS8也增加了两种细胞系中的上皮-间质转化（EMT）水平、细胞增殖和细胞活力。相反，敲低Eps8表达降低了两种细胞系中的EMT水平、细胞增殖和细胞活力。此外，抑制Ras/JAK/PI3K信号通路可逆转EPS8诱导的EMT激活。体内动物研究也证实了Eps8表达在前列腺癌进展中的关键作用。因此，我们建议通过敲低Eps8的表达来靶向它，作为前列腺癌治疗的一种有前景的治疗方法。
