Abstract 29P
Background
The E3 ligase HUWE1 is a key regulator of the DNA damage response, transcription, autophagy, apoptosis and metabolism in a variety of cancers. Due to its pivotal role in conferring substrate specificity, HUWE1 has attracted enormous attention as a promising anticancer drug target. In this study, we have studied the role of HUWE1 in triple-negative breast cancer (TNBC) cell lines and evaluated its role on aerobic glycolysis which is upregulated in cancer cells and immune modulatory markers for their roles in immunotherapy. TNBC subtype neither express hormone receptors nor Her2/neu. TNBC are highly aggressive, with poor prognosis and no well-defined treatment regimen. Therefore, considering HUWE1 as an oncogene its role has been explored on glucose metabolism and immune modulation in TNBC cell lines.
Methods
Two TNBC cell lines i.e., MDA-MB-231 and MDA-MB-468 were used in the present study. These cell lines were treated with HUWE1 inhibitor: BI8622 for 24 h and the effect of inhibition was seen on its substrate (c-myc), aerobic glycolytic (HK-2, GLUT-1) and immune checkpoint markers (PDL-1, CD-47) using western blotting approach. Wound healing assays and clonogenic assays were also performed in BI8622 treated cells to check the effects of HUWE1 inhibition on migration and colony forming ability of TNBC cells in both the cell lines.
Results
As expected, there was a decrease in the protein expression levels of c-myc after the HUWE1 inhibition. Furthermore, there was decrease in protein expression of glycolytic markers i.e. HK-2 and GLUT-1 as well as immuno modulatory markers i.e. PDL-1 and CD-47. Additionally, the HUWE1 inhibition in TNBC cells was positively associated with the inhibition of migration and clonogenic potential.
Conclusions
In this study for the first time, we have demonstrated that HUWE1 acts as a tumor suppressor in TNBC by regulating the glucose metabolism and immune checkpoint inhibitors. HUWE1 inhibition could functionally suppress TNBC development possibly by regulating aerobic glycolysis and immune checkpoints through c-myc.
Clinical trial identification
Editorial acknowledgement
Funded by Indian Council of Medical Research (ICMR), New Delhi, India.
Legal entity responsible for the study
The authors.
Funding
Indian Council of Medical research (ICMR).
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
228P - Real-world data on dose adjustment of cabozantinib in advanced renal cell carcinoma
Presenter: Hemavathi Baskarane
Session: Poster Display
Resources:
Abstract
229P - The application of diffusion kurtosis imaging in predicting muscle invasion of bladder cancer: A comparison with conventional DWI
Presenter: Shuai Jiang
Session: Poster Display
Resources:
Abstract
230P - Oncological outcomes between partial cystectomy and radical cystectomy in solitary muscle invasive bladder cancer with downgraded T stage
Presenter: Ming Wei Hsu
Session: Poster Display
Resources:
Abstract
231P - BMI-predicted progression-free survival after pembrolizumab therapy for urothelial cancer: Asian version of BMI classification is suitable for Asian patients
Presenter: mirii harada
Session: Poster Display
Resources:
Abstract
232P - The immunosuppressive features of the 20S Proteasome β-subunit gene family in von Hippel-Lindau (VHL)-mutated clear cell renal cell carcinoma (ccRCC): A TCGA-based bioinformatics study
Presenter: Saja Alzghoul
Session: Poster Display
Resources:
Abstract
233P - The crosstalk between PBRM1 loss and tumor immune microenvironment (TIME) of clear cell renal cell carcinoma (ccRCC): A possible interconnection to immunotherapy response
Presenter: Ahmed Al Sharie
Session: Poster Display
Resources:
Abstract
235P - Do FGFR2 and 3 proteins have a role in the prognosis of urothelial bladder carcinoma?
Presenter: Alshimaa Al Hanafy
Session: Poster Display
Resources:
Abstract
236P - The effects of chemotherapy on body composition in patients with advanced urothelial carcinoma
Presenter: KOSUKE KITAMURA
Session: Poster Display
Resources:
Abstract
237P - Real-world analysis of adjuvant nivolumab in resected urothelial cancer: A single institute study in Taiwanese patients
Presenter: Mu-Hsin Chang
Session: Poster Display
Resources:
Abstract
238P - Enfortumab-vedotin for metastatic urothelial carcinoma refractory to platinum-based chemotherapy and immune checkpoint inhibitors: A single institution experience
Presenter: Yuki Endo
Session: Poster Display
Resources:
Abstract