MUC1 triggers lineage plasticity of Her2 positive mammary tumors View Full Text


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Article Info

DATE

2022-04-23

AUTHORS

Zhi Pang, Xinran Dong, Huayun Deng, Chengzhi Wang, Xiaodong Liao, Chunhua Liao, Yahui Liao, Weidong Tian, Jinke Cheng, Guoqiang Chen, Haiying Yi, Lei Huang

ABSTRACT

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 MUC1/HER2 in the development of breast cancer has not been fully illustrated. Following analysis of public microarray datasets that revealed a correlation between double MUC1 and HER2 positivity and 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 conferred a growth advantage and promoted the development of spontaneous mammary tumors. Genomic analysis revealed that enforced expression of MUC1-CD and Her2 induces mammary tumor lineage plasticity, which is supported by gene reprogramming and mammary stem cell enrichment. Through gain- and loss-of-function strategies, we show that coexpression of Her2 and MUC1-CD is associated with downregulation of tricarboxylic acid (TCA) cycle genes in tumors. Importantly, the reduction in TCA cycle genes induced by MUC1-CD was found to be significantly connected to poor prognosis in HER2+ breast cancer patients. In addition, MUC1 augments the Her2 signaling pathway by inducing Her2/Egfr dimerization. These findings collectively demonstrate the vital role of MUC1-CD/Her2 collaboration in shaping the mammary tumor landscape and highlight the prognostic and therapeutic implications of MUC1 in patients with HER2+ breast cancer. More... »

PAGES

3064-3078

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41388-022-02320-y

    DOI

    http://dx.doi.org/10.1038/s41388-022-02320-y

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/35461328


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