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
5638 - Incidence of Vascular Thromboembolism Events in Cancer Patients Receiving Immunotherapy: A Single Institution Experience.
Presenter: Laura Gutiérrez Sainz
Session: Poster Display session 1
Resources:
Abstract
5182 - High Incidence of Venous Thromboembolic Events (VTE) in Patients with Diffuse Large B-Cell Lymphoma.
Presenter: Alaa Abufara
Session: Poster Display session 1
Resources:
Abstract
1504 - Weight Loss over Time in Non-Small Cell Lung Cancer: Results from a Landmark Analysis of 800+ Prospectively-Treated Patients
Presenter: Jennifer Le-rademacher
Session: Poster Display session 1
Resources:
Abstract
3972 - The prognostic significance of preoperative nutritional status in resected pancreatic ductal adenocarcinoma (PDAC).
Presenter: Salvatore Paiella
Session: Poster Display session 1
Resources:
Abstract
2313 - Impact of Timing and Technique of Gastrostomy Placement on the Outcome of Patients (pts) with Head and Neck Cancer (HNC)
Presenter: M Julia Lostes Bardaji
Session: Poster Display session 1
Resources:
Abstract
5219 - Clinical & nutritional determinants of quality of life in patients with incurable cancer
Presenter: Louise Daly
Session: Poster Display session 1
Resources:
Abstract
4075 - Loss of skeletal muscle mass during palliative chemotherapy is a poor prognostic factor in patients with advanced gastric cancer
Presenter: In Gyu Hwang
Session: Poster Display session 1
Resources:
Abstract
4159 - Impact of nutritional derangement on treatment outcome in advanced non-small-cell lung cancer (A-NSCLC) patients (pts).
Presenter: Ilaria Trestini
Session: Poster Display session 1
Resources:
Abstract
1210 - Sarcopenia and pretreatment anemia as prognostic factors for patients with localized muscle invasive bladder cancer treated by neoadjuvant chemotherapy and radical cystectomy
Presenter: Emilien Billon
Session: Poster Display session 1
Resources:
Abstract
2490 - Gender effect on the pharmacokinetics (PK) and pharmacodynamics (PD) of anamorelin (ANAM) in healthy volunteers and cancer patients with cachexia
Presenter: Stein Kaasa
Session: Poster Display session 1
Resources:
Abstract