EMILIN-1 Suppresses Cell Proliferation through Altered Cell Cycle Regulation in Head and Neck Squamous Cell Carcinoma
Issued Date
2025-05-01
Resource Type
ISSN
00029440
eISSN
15252191
Scopus ID
2-s2.0-105002408489
Pubmed ID
39892781
Journal Title
American Journal of Pathology
Volume
195
Issue
5
Start Page
995
End Page
1012
Rights Holder(s)
SCOPUS
Bibliographic Citation
American Journal of Pathology Vol.195 No.5 (2025) , 995-1012
Suggested Citation
Chanpanitkitchote P., Nuanpirom J., Pongsapich W., Asavapanumas N., Mendler S., Wiesmann N., Brieger J., Jinawath N. EMILIN-1 Suppresses Cell Proliferation through Altered Cell Cycle Regulation in Head and Neck Squamous Cell Carcinoma. American Journal of Pathology Vol.195 No.5 (2025) , 995-1012. 1012. doi:10.1016/j.ajpath.2025.01.010 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109618
Title
EMILIN-1 Suppresses Cell Proliferation through Altered Cell Cycle Regulation in Head and Neck Squamous Cell Carcinoma
Corresponding Author(s)
Other Contributor(s)
Abstract
Extracellular matrix (ECM) proteins play an important role in the pathological processes of tumor development and progression. Elastic microfibril interface located protein-1 (EMILIN-1), an ECM glycoprotein, is linked to cell adhesion and migration. It was identified from head and neck squamous cell carcinoma (HNSCC) tissues that down-regulated EMILIN-1. It is associated with an increased risk of secondary primary malignancy development in HNSCC and hypothesized to function as a tumor suppressor in HNSCC. This study showed that EMILIN-1 expression in HNSCC tissues was specific to the stromal area, and secreted-EMILIN-1 level was higher in fibroblasts isolated from HNSCC tissues than in HNSCC cells. EMILIN-1 overexpression decreased cell proliferation, migration, and invasion in FaDu and CAL27 cells. Knockdown of EMILIN-1 in HNSCC cancer-associated fibroblasts induced cell proliferation and migration. The conditioned medium from EMILIN-1 knockdown cancer-associated fibroblasts increased HNSCC cell proliferation, and the co-culture system enhanced cancer cell migration and invasion. RNA-sequencing analysis revealed that the cell cycle and aurora kinase signaling were the most significant enrichment pathways, confirmed at the protein level. Furthermore, in an in ovo chick chorioallantoic membrane model, overexpression of EMILIN-1 in FaDu cells reduced tumor size and Ki-67–positivity and increased cleaved caspase-3–positive cells. These findings suggest that EMILIN-1 suppresses HNSCC growth partly through the down-regulation of cell cycle and aurora kinase signaling pathways.