Abstract 3235
Background
Ovarian cancer is the most lethal gynecological cancer and the biological mechanisms remains unclear. The prevalence of abnormal fucosylation has been reported to be closely related to cancer progression and prognosis. It was reported that only FUT3 and/or FUT6 in the α 1-3/4 fucosyltransferase subfamily were required for TGF-β-mediated epithelial-to-mesenchymal transition (EMT) in colorectal cancer. However, it was also reported that the α 1-6 fucosyltransferase FUT8 facilitated TGF-β binding to receptor and stimulated the EMT in breast cancer. As an α 1-3 fucosyltransferase distinct from the α 1-3/4 and 1-6 fucosyltransferase subfamily, the role of FUT11 in ovarian cancer development is less understood.
Methods
FUT11 was identified as a novel oncogene related with the EMT process in ovarian cancer by bioinformatic analysis and real-time PCR. The transwell chamber assays were used to examine the changes of the invasion and migration ability after FUT11 knocked-down by siRNA treatment in ovarian cancer cells SK-OV-3 and HEY. Western-blot was usd to determine the changes of EMT genes by FUT11 depletion in response to TGF-β 1. Furthermore, expression and location of R-Smads and Co-Smad were analyzed by western blot and immunofluorescence assay, to evaluate the impact of FUT11 depletion on the TGF-β/Smad pathway.
Results
FUT11 was highly expressed in ovarian cancer, and increased FUT11 expression was significantly correlated with poor survival of the ovarian patients. FUT11 depletion impaired the invasion and migration of the ovarian cancer cell lines, through regulation of the TGF-β 1-induced EMT process. These inhibitory effect was due to downregulation of the expression of SMAD2 and SMAD3, as well as prevention of their translocation from cytoplasm to nucleus. Although expression of SMAD4 were slightly affected, their translocation from cytoplasm to nucleus were inhibited by FUT11 depletion.
Conclusions
FUT11 promotes invasion and migration of ovarian cancer through regulation of the TGF-β 1-induced EMT process. FUT11 affects the response to TGF-β 1 by regulation of the expression level of R-Smads and Co-Smad, as well as their translocation from cytoplasm to nucleus.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Beijing Obstetrics and Gynecology Hospital, Capital Medical University.
Funding
The National Natural Science Foundation of China (81502353 & 81672838), Beijing Municipal Science & Technology Commission (No. Z181100001718193), and Beijing Obstetrics and Gynecology Hospital, Capital Medical University (FCYY201713).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
4852 - Impact of routine screening and preemptive treatment on hepatitis B virus reactivation (HBVr) in patients receiving chemotherapy
Presenter: Celine Marty
Session: Poster Display session 1
Resources:
Abstract
5225 - The uptake, patient satisfaction and efficacy of scalp cooling among patients receiving chemotherapy in an Irish oncology day ward.
Presenter: William Maher
Session: Poster Display session 1
Resources:
Abstract
1901 - Placebo adverse events (AEs) in targeted and immune cancer therapy in the adjuvant and advanced setting: A systematic review and meta-analysis
Presenter: Diego Enrico
Session: Poster Display session 1
Resources:
Abstract
3258 - Reduced antibody levels and high seronegativity rates against vaccine preventable diseases pose a risk factor for infections in patients with solid and hematologic cancers
Presenter: Angela Guzek
Session: Poster Display session 1
Resources:
Abstract
3211 - Prognostic Factors Influencing Outcome After Therapy With Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin's Lymphoma
Presenter: Veselina Goranova - Marinova
Session: Poster Display session 1
Resources:
Abstract
4949 - Phase I Study of CC-90010 in Patients With Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma (R/R NHL)
Presenter: Victor Moreno
Session: Poster Display session 1
Resources:
Abstract
2271 - Pretreatment coagulation factors related to prognosis in patients with natural killer/T cell lymphoma
Presenter: Yue Chai
Session: Poster Display session 1
Resources:
Abstract
4335 - Diffuse large B cell lymphoma in the elderly. A retrospective analysis of standard versus alternative treatments
Presenter: Irene Sillero
Session: Poster Display session 1
Resources:
Abstract
5117 - MIPI as a superior prognostic tool in Mantle Cell Lymphoma compared to monocyte-lymphocyte, neutrophil-lymphocyte and platelet-lymphocyte ratios
Presenter: Filipa Macedo
Session: Poster Display session 1
Resources:
Abstract
5135 - Dose adjustment of chemotherapy in aggressive lymphoma using automated and standardized analysis and evaluation of DNA double strand breaks
Presenter: Julia Schröder
Session: Poster Display session 1
Resources:
Abstract