American Association for Cancer Research
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Figure S2 from Identification of MUC1-C as a Target for Suppressing Progression of Head and Neck Squamous Cell Carcinomas

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journal contribution
posted on 2024-05-14, 14:20 authored by Ayako Nakashoji, Naoki Haratake, Atrayee Bhattacharya, Weipu Mao, Kangjie Xu, Keyi Wang, Tatsuaki Daimon, Hiroki Ozawa, Keisuke Shigeta, Atsushi Fushimi, Nami Yamashita, Yoshihiro Morimoto, Mototsugu Shimokawa, Shin Saito, Ann Marie Egloff, Ravindra Uppaluri, Mark D. Long, Donald Kufe

MUC1-C regulates the type I and IFN pathways in CAL27 and HSC3 cells.


HHS | NIH | National Cancer Institute (NCI)



The MUC1-C protein is aberrantly expressed in adenocarcinomas of epithelial barrier tissues and contributes to their progression. Less is known about involvement of MUC1-C in the pathogenesis of squamous cell carcinomas (SCC). Here, we report that the MUC1 gene is upregulated in advanced head and neck SCCs (HNSCC). Studies of HNSCC cell lines demonstrate that the MUC1-C subunit regulates expression of (i) RIG-I and MDA5 pattern recognition receptors, (ii) STAT1 and IFN regulatory factors, and (iii) downstream IFN-stimulated genes. MUC1-C integrates chronic activation of the STAT1 inflammatory pathway with induction of the ∆Np63 and SOX2 genes that are aberrantly expressed in HNSCCs. In extending those dependencies, we demonstrate that MUC1-C is necessary for NOTCH3 expression, self-renewal capacity, and tumorigenicity. The findings that MUC1 associates with ∆Np63, SOX2 and NOTCH3 expression by single-cell RNA sequencing analysis further indicate that MUC1-C drives the HNSCC stem cell state and is a target for suppressing HNSCC progression. This work reports a previously unrecognized role for MUC1-C in driving STAT1-mediated chronic inflammation with the progression of HNSCC and identifies MUC1-C as a druggable target for advanced HNSCC treatment.