Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells

Wei-Lun Huang; Sih-Han Chen; Richard Chen-Yu Wu; Hsing-Cha Mai; Chun-Hsien Wu; Pei-Fang Hsieh; See-Tong Pang; Victor Chia-Hsiang Lin

doi:10.62347/YQWJ7498

Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells

Am J Cancer Res. 2024 Oct 15;14(10):4717-4730. doi: 10.62347/YQWJ7498. eCollection 2024.

Authors

Wei-Lun Huang^{1

2

3}, Sih-Han Chen^{1

2

3

4}, Richard Chen-Yu Wu^{1

2

5}, Hsing-Cha Mai^{2

3

6}, Chun-Hsien Wu^{1

2

3}, Pei-Fang Hsieh^{1

7}, See-Tong Pang^{8

9}, Victor Chia-Hsiang Lin^{1

3}

Affiliations

¹ Division of Urology, Department of Surgery, E-Da Hospital Kaohsiung 824, Taiwan.
² Department of Nursing, I-Shou University Kaohsiung 840, Taiwan.
³ School of Medicine, College of Medicine, I-Shou University Kaohsiung 840, Taiwan.
⁴ Graduate Institute of Medicine, Medical College, I-Shou University Kaohsiung, Taiwan.
⁵ Department of Information Engineering, I-Shou University Kaohsiung 840, Taiwan.
⁶ Department of Urology, E-Da Cancer Hospital Kaohsiung, Taiwan.
⁷ Department of Medical Laboratory Science and Biotechnology, Chung-Hua University of Medical Technology Tainan 300, Taiwan.
⁸ Graduate Institute of Clinical Medical Science, College of Medicine, Chang Gung University 333 Taiwan.
⁹ Division of Urology, Department of Surgery, Chang Gung Memorial Hospital, Linkou Branch 333 Taiwan.

Abstract

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.

Keywords: Epidermal growth factor receptor pathway substrate 8; cancer progression; castration-resistant; epithelial-to-mesenchymal transition; prostate cancer.