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Series GSE230179 Query DataSets for GSE230179
Status Public on Apr 30, 2023
Title HER2∆16 Engages ENPP1 To Promote an Immune Cold Microenvironment in Breast Cancer [tumor]
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary 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.
Overall design End point tumors harvested and flash frozen. RNA was extracted and sequenced
Contributor(s) Sherif A, Jonathan B, Hailey P, Tarek T, Dongmei Z, Virginie S, Chen L, Gabriella J, Vincent L, Robin L, Hellen K, Vasilios P, Logan W, Mark B, Heikki J, Morag P, Philippe R, William M
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Submission date Apr 20, 2023
Last update date Apr 30, 2023
Contact name Sherif Samer Attalla
Organization name McGill
Department Goodman Cancer Institute
Lab Muller lab
Street address 1160 Ave. Pine W
City Montreal
State/province Quebec
ZIP/Postal code H3A1A3
Country Canada
Platforms (1)
GPL17021 Illumina HiSeq 2500 (Mus musculus)
Samples (10)
GSM7191269 Tumors from EIC mouse [EIC5527]
GSM7191270 Tumors from EIC mouse [EIC6011]
GSM7191271 Tumors from EIC mouse [EIC6017]
BioProject PRJNA957790

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Supplementary file Size Download File type/resource
GSE230179_DEG.txt.gz 5.5 Mb (ftp)(http) TXT
GSE230179_FPKM_all_samples.xls.gz 3.0 Mb (ftp)(http) XLS
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Raw data are available in SRA
Processed data are available on Series record

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