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| Status |
Public on Mar 10, 2022 |
| Title |
MUC1 triggers lineage plasticity of Her2 positive mammary tumor |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The aberrant overexpression of mucin 1 (MUC1) and human epidermal growth factor receptor 2 (HER2) are often observed in breast cancer. However, the role of concomitant of MUC1/HERR2 in the development of breast cancer has not been fully illustrated. Following analysis public microarray datasets that revealed a correlation of double positive of MUC1 and HER2 to a worse clinical outcome, we generated a mouse model overexpressing both Her2 and MUC1 cytoplasmic domain (MUC1-CD) to investigate their interaction in mammary carcinogenesis. Coexpression of Her2 and MUC1-CD confers growth advantage and promotes the development of spontaneous mammary tumors. Genomic analysis uncovers that enforced expression of MUC1-CD and Her2 induces mammary tumor lineage plasticity which is supported by gene reprogramming and mammary stem cell enrichment. With gain- and loss-of function strategies, we show that coexpression of Her2 and MUC1-CD was associated with down-regulation of TCA cycle genes in tumors. Importantly, the reduction of TCA cycle genes induced by MUC1-CD is is significantly connected to the poor prognosis in HER2+ breast cancer patients. In addition, MUC1 augments Her2 signaling pathway by inducing Her2/Egfr dimerization. These findings collectively demonstrate the vital role of MUC1-CD/Her2 collaboration in shaping mammary tumor landscape and highlight the prognostic and therapeutic implication of MUC1 in patients with Her2+ breast cancer.
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| Overall design |
Two replicates for MUC1WT/Her2+ and four for MUC1CD+/Her2+. Each pair included one tumor tissue and one normal adjacent tissue.
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| Contributor(s) |
Huang L, Pang Z |
| Citation(s) |
35461328 |
| Submission date |
Mar 09, 2022 |
| Last update date |
May 13, 2022 |
| Contact name |
Zhi Pang |
| E-mail(s) |
pang.zhi@zs-hospital.sh.cn
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| Organization name |
Zhongshan Hospital,Fudan University
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| Department |
Liver Cancer Institute,
|
| Street address |
180 fenglin road
|
| City |
shanghai |
| ZIP/Postal code |
200032 |
| Country |
China |
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| Platforms (1) |
| GPL15887 |
NimbleGen Mouse gene expression array [100718_MM9_EXP] (gene-level version) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA814266 |
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