Cancers, Vol. 12, Pages 468: A Comprehensive Analysis of FUT8 Overexpressing Prostate Cancer Cells Reveals the Role of EGFR in Castration Resistance

Cancers, Vol. 12, Pages 468: A Comprehensive Analysis of FUT8 Overexpressing Prostate Cancer Cells Reveals the Role of EGFR in Castration Resistance Cancers doi: 10.3390/cancers12020468 Authors: Naseruddin Höti Tung-Shing Lih Jianbo Pan Yangying Zhou Ganglong Yang Ashely Deng Lijun Chen Mingmimg Dong Ruey-Bing Yang Cheng-Fen Tu Michael C. Haffner Qing Kay Li Hui Zhang The emergence of castration-resistance is one of the major challenges in the management of patients with advanced prostate cancer. Although the spectrum of systemic therapies that are available for use alongside androgen deprivation for treatment of castration-resistant prostate cancer (CRPC) is expanding, none of these regimens are curative. Therefore, it is imperative to apply systems approaches to identify and understand the mechanisms that contribute to the development of CRPC. Using comprehensive proteomic approaches, we show that a glycosylation-related enzyme, alpha (1,6) fucosyltransferase (FUT8), which is upregulated in CRPC, might be responsible for resistance to androgen deprivation. Mechanistically, we demonstrated that overexpression of FUT8 resulted in upregulation of the cell surface epidermal growth factor receptor (EGFR) and corresponding downstream signaling, leading to increased cell survival in androgen-depleted conditions. We studied the coregulatory mechanisms of EGFR and FUT8 expression in CRPC xenograft models and found that castration induced FUT8 overexp...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research