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
239P - Elevated baseline C-reactive protein is a prognostic indicator for OS in patients with metastatic non clear cell renal cell carcinoma treated with systemic therapy
Presenter: Ryuichi Mizuno
Session: Poster Display
Resources:
Abstract
240P - Efficacy and safety of first-line combination therapy with ipilimumab + nivolumab for metastatic renal cell carcinoma in a single institution in Japan
Presenter: Naoya Nagaya
Session: Poster Display
Resources:
Abstract
241P - First-line cabozantinib in metastatic renal cell carcinoma (mRCC): A real-world exploratory study from eastern India
Presenter: Tamojit Chaudhuri
Session: Poster Display
Resources:
Abstract
244P - Clinicopathologic feature and treatment outcome of metastatic non clear cell kidney cancer: A single centre experience from India
Presenter: Somnath Roy
Session: Poster Display
Resources:
Abstract
245P - The role of TGF-β in the formation of the protumor phenotype of circulating neutrophils at different stages of renal cancer
Presenter: Ilseya Myagdieva
Session: Poster Display
Resources:
Abstract
246P - Impact of renal impairment on first-line treatment in metastatic urothelial cancer
Presenter: Stephanie Wakeling
Session: Poster Display
Resources:
Abstract
247P - Adjuvant chemoradiotherapy in the management of bladder adenocarcinoma compared to multiple treatment modalities
Presenter: Othman Mohammed
Session: Poster Display
Resources:
Abstract
248P - Screening zinc homeostasis-related genes identifies metallothionein 1H (MT1H) as a potential prognostic biomarker in clear cell renal cell carcinoma (ccRCC)
Presenter: Eyad Al Masoud
Session: Poster Display
Resources:
Abstract
249P - The prognostic utility of Progestogen associated Endometrial protein (PAEP) gene expression in clear cell renal cell carcinoma (ccRCC)
Presenter: Leen Lataifeh
Session: Poster Display
Resources:
Abstract
250P - Impact of adjuvant chemo(radio)therapy in stage I/II testicular seminoma
Presenter: Mahmoud Eleisawy
Session: Poster Display
Resources:
Abstract