CMTM4 regulates epithelial–mesenchymal transition and PD‐L1 expression in head and neck squamous cell carcinoma
| Autor: | Shu-Jin Li, Yuan-Tong Liu, Hao Li, Zhi-Jun Sun, Jun-Jie Zhou, De-Run Chen, Lei Chen |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Small interfering RNA Epithelial-Mesenchymal Transition Biology B7-H1 Antigen Metastasis 03 medical and health sciences 0302 clinical medicine Cancer stem cell Cell Line Tumor PD-L1 Biomarkers Tumor Tumor Microenvironment medicine Humans Epithelial–mesenchymal transition Molecular Biology Protein kinase B Gene knockdown MARVEL Domain-Containing Proteins Squamous Cell Carcinoma of Head and Neck medicine.disease Immunohistochemistry Head and neck squamous-cell carcinoma Gene Expression Regulation Neoplastic 030104 developmental biology Gene Knockdown Techniques Lymphatic Metastasis 030220 oncology & carcinogenesis Cancer research biology.protein |
| Zdroj: | Molecular Carcinogenesis. 60:556-566 |
| ISSN: | 1098-2744 0899-1987 |
| Popis: | The epithelial-mesenchymal transition (EMT) is a pivotal step involved in cancer recurrence and metastasis. In addition, the activation of the EMT program can induce a cancer stem cell (CSC)-like phenotype and programmed death-ligand 1 (PD-L1) expression in head and neck squamous cell carcinoma (HNSCC). The CMTM family has reported as an important regulator in this process. Here, we investigated the role of CMTM4 in HNSCC. We indicated that CMTM4 was overexpressed in human and mouse HNSCC samples and in HNSCC cell lines by immunohistochemistry and Western blot. A high expression level of CMTM4 was correlated with advanced lymph node metastasis and a negative prognosis. CMTM4-knockdown by small interfering RNA downregulated the EMT process and inhibited the migration and invasion abilities of tumor cells. Moreover, knockdown of CMTM4 decreased CSC-associated markers via the protein kinase B pathway. Notably, CMTM4-knockdown inhibited the expression of interferon-γ induced PD-L1 in HNSCC cells. A positive correlation was found between CMTM4 expression and CD8+ and PD-1+ cell density in the stroma. Our findings indicated that CMTM4 may play an important role in regulating EMT/CSC phenotypes and PD-L1 expression. This study may reinforce the interest in CMTM4 as a potential target for the prognosis and treatment of HNSCC. |
| Databáze: | OpenAIRE |
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