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A Comprehensive Analysis of FUT8 Overexpressing Prostate Cancer Cells Reveals the Role of EGFR in Castration Resistance
- Source :
- Cancers, Volume 12, Issue 2, Cancers, Vol 12, Iss 2, p 468 (2020)
- Publication Year :
- 2020
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2020.
-
Abstract
- 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 overexpression associated with increased expression of EGFR. Taken together, our findings suggest a crucial role played by FUT8 as a mediator in switching prostate cancer cells from nuclear receptor signaling (androgen receptor) to the cell surface receptor (EGFR) mechanisms in escaping castration-induced cell death. These findings have clinical implication in understanding the role of FUT8 as a master regulator of cell surface receptors in cancer-resistant phenotypes.
- Subjects :
- Cancer Research
alpha (1,6) fucosyltransferase
medicine.drug_class
urologic and male genital diseases
lcsh:RC254-282
Article
03 medical and health sciences
Prostate cancer
0302 clinical medicine
proteomics
Castration Resistance
Downregulation and upregulation
Cell surface receptor
Medicine
glycoproteomics
Epidermal growth factor receptor
030304 developmental biology
0303 health sciences
biology
business.industry
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Androgen
medicine.disease
prostate cancer
3. Good health
Androgen receptor
Oncology
Nuclear receptor
030220 oncology & carcinogenesis
Cancer research
biology.protein
business
Subjects
Details
- Language :
- English
- ISSN :
- 20726694
- Database :
- OpenAIRE
- Journal :
- Cancers
- Accession number :
- edsair.doi.dedup.....3335b1a91f435d8c50ed9ee604052f8a
- Full Text :
- https://doi.org/10.3390/cancers12020468