Abstract 51P
Background
STING (STimulator of INterferon Genes) is a pattern recognition receptor detecting cytoplasmic nucleic acids and transmits signals that activate host innate immune responses. It has been found to be involved in anti‐microbial immunity, autoimmune disorder and tumorigenesis. Thus, the acknowledgement of the cellular regulation of STING is important. However, transcriptional regulation of STING and its role in tumor development has not been reported.
Methods
STNF expressing vector was constructed and used to identify the STNF regulatory function of STING. Small interfering RNA was used to silence STNF expression. For the first time, full length of STING promoter was constructed with luciferase reporter which enabled quick and semi-quantitative of STING promoter activity. The bc-GenExMiner v4.2 database was used to evaluate the expression and prognostic merit of STNF and STING in breast cancer (BC). Western blot, RT-qPCR and CCK-8 assay were used to detect STING expression and BC cell growth.
Results
We have identified a novel negative regulator of STING (STNF). The effect of STNF appeared to be at the transcriptional level of STING since STNF could suppress the promoter activity of STING. STNF was up-regulated in breast cancer (BC) and associated with poor prognosis of BC patients. Silencing STNF or pharmacologically inhibiting STNF promoted STING expression and suppressed BC growth. STING down-regulation was observed in different types of BC and restoration of STING expression resulted in broad BC inhibition.
Conclusions
Our study demonstrated an unprecedented strategy used by breast tumor to escape from STING mediated tumor suppression. The identification of a novel STING regulator will provide insights for novel anti-tumor strategy against BC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Xiao-Fang Yu.
Funding
National Youth Science Fund Project: 81701988(C0025181).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
196P - The tolerability and efficacy of FOLFIRINOX in gastro-oesophageal carcinoma
Presenter: Nicholas Travers
Session: Poster display session
Resources:
Abstract
197TiP - GLOW: Zolbetuximab + CAPOX compared with placebo + CAPOX as first-line treatment for patients with Claudin18.2+/HER2– Locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma: A randomized phase III study
Presenter: Rui-Hua Xu
Session: Poster display session
Resources:
Abstract
198TiP - SPOTLIGHT: Comparison of zolbetuximab or placebo + mFOLFOX6 as first-line treatment in patients with claudin18.2+/HER2– locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma (GEJ): A randomized phase III study
Presenter: Kensei Yamaguchi
Session: Poster display session
Resources:
Abstract
199TiP - Phase III (COSMIC-312) study of cabozantinib (C) in combination with atezolizumab (A) vs sorafenib (S) in patients (pts) with advanced hepatocellular carcinoma (aHCC) who have not received previous systemic anticancer therapy
Presenter: Thomas Yau
Session: Poster display session
Resources:
Abstract
200P - Apalutamide (APA) plus androgen deprivation therapy (ADT) for metastatic castration-sensitive prostate cancer (mCSPC): Analysis of pain and fatigue in the TITAN study
Presenter: Byung Ha Chung
Session: Poster display session
Resources:
Abstract
201P - Efficacy and safety of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC) in the ARAMIS trial
Presenter: Jacob See-tong Pang
Session: Poster display session
Resources:
Abstract
202P - What is the best first-line therapy for metastatic castration-sensitive prostate cancer in 2019? A network meta-analysis
Presenter: Tsz Him So
Session: Poster display session
Resources:
Abstract
203P - Long term outcomes of 2-weekly docetaxel in metastatic high-volume hormone sensitive prostate cancer
Presenter: Suhas Singla
Session: Poster display session
Resources:
Abstract
204P - The effect of radium-223 therapy in agent orange related veterans with metastatic castrate resistance prostate carcinoma (CRPC)
Presenter: Andrew Liman
Session: Poster display session
Resources:
Abstract
205P - Treatment pattern and outcomes of radium-223 (Ra223) in metastatic castration resistant prostate cancer (mCRPC): Retrospective cohort analysis from Hong Kong
Presenter: Darren Poon
Session: Poster display session
Resources:
Abstract