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
5465 - Proof of concept clinical study by US-guided intratumor injection of VCN-01, an oncolytic adenovirus expressing hyaluronidase in patients with pancreatic cancer
Presenter: Manuel Hidalgo
Session: Poster Display session 1
Resources:
Abstract
2555 - A Phase 1a/b first-in-human, open-label, dose-escalation, safety, PK and PD study of TP-0903 in solid tumors
Presenter: John Sarantopoulos
Session: Poster Display session 1
Resources:
Abstract
3533 - First in human phase 1/2a study of PEN-866, a Heat Shock Protein 90 (HSP90) ligand – SN38 conjugate for patients with advanced solid tumors: Phase 1 results
Presenter: Johanna Bendell
Session: Poster Display session 1
Resources:
Abstract
4114 - A Phase I Open-Label, Non-Randomized Study of Recombinant Super-Compound Interferon (rSIFN-co) In Patients with Advanced Solid Tumors
Presenter: Amanda Seet
Session: Poster Display session 1
Resources:
Abstract
2537 - Evaluation of Pharmacodynamic (PD) Biomarkers in Advanced Cancer Patients Treated with Oxidative Phosphorylation (OXPHOS) Inhibitor, OPC-317 (OPC)
Presenter: Jie Qing Eu
Session: Poster Display session 1
Resources:
Abstract
5764 - Pharmacokinetic (PK) assessment of BT1718: A phase 1/2a study of BT1718, a first in class Bicycle Toxin Conjugate (BTC), in patients (pts) with advanced solid tumours
Presenter: Natalie Cook
Session: Poster Display session 1
Resources:
Abstract
2683 - A phase I open label dose escalation trial evaluating VT1021 in patients with advanced solid tumors.
Presenter: Wael Harb
Session: Poster Display session 1
Resources:
Abstract
3609 - Interim Results from Trial of SL-801, a Novel XPO-1 Inhibitor, in Patients with Advanced Solid Tumors
Presenter: Judy Wang
Session: Poster Display session 1
Resources:
Abstract
3485 - Phase 1 Trial of Fruquintinib in Patients with Advanced Solid Tumors: Results of the Dose Escalation Phase
Presenter: Andrea Wang-Gillam
Session: Poster Display session 1
Resources:
Abstract
4085 - A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-601 in Patients with Advanced Solid Tumors
Presenter: Anthony Tolcher
Session: Poster Display session 1
Resources:
Abstract