Transcriptomics

Dataset Information

0

HER2∆16 Engages ENPP1 To Promote an Immune Cold Microenvironment in Breast Cancer [cell line]


ABSTRACT: The tumor immune microenvironment (TIME) is a critical determinant of therapeutic response. However, the mechanisms regulating its modulation are not fully understood. HER2D16, an oncogenic splice variant of the human epidermal growth factor receptor (HER2), has been implicated in breast cancer and other tumor types as a driver of tumorigenesis and metastasis. Nevertheless, the underlying mechanisms of HER2Δ16-mediated oncogenicity remain poorly understood. Here, we show that HER2∆16 expression is not exclusive to the clinically HER2+ subtype and is associated with a poor clinical outcome in breast cancer. To understand how HER2 variants modulate the tumor microenvironment, we generated transgenic mouse models expressing either proto-oncogenic HER2 or HER2D16 in the mammary epithelium. We found that HER2∆16 tumors are immune cold, characterized by low immune infiltrate and an altered cytokine profile. Using an epithelial cell surface proteomic approach, we identified ENPP1 as a functional regulator of the immune cold microenvironment. We generated a knock-in model of HER2Δ16 under the endogenous promoter to understand the role of ENPP1 in aggressive HER2+ breast cancer. Knockdown of ENPP1 in HER2Δ16-derived tumor cells resulted in decreased tumor growth that was correlated with increased T-cell infiltration. These findings suggest that HER2Δ16-dependent ENPP1 activation is associated with aggressive HER2+ breast cancer through its immune modulatory function. Our study provides a better understanding of the mechanisms underlying HER2Δ16-mediated oncogenicity and highlights ENPP1 as a potential therapeutic target in aggressive HER2+ breast cancer.

ORGANISM(S): Mus musculus

PROVIDER: GSE230272 | GEO | 2023/04/30

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2023-04-30 | GSE230179 | GEO
2024-01-08 | GSE248288 | GEO
2023-08-07 | GSE233659 | GEO
2024-01-15 | PXD041186 | Pride
2022-01-17 | GSE193691 | GEO
2016-12-09 | GSE75688 | GEO
2024-10-25 | GSE264328 | GEO
2015-11-09 | E-GEOD-69042 | biostudies-arrayexpress
2014-08-22 | E-GEOD-55070 | biostudies-arrayexpress
| PRJNA683665 | ENA