Abstract
Oral squamous cell carcinoma (OSCC) is one of the most common types of malignant tumor. Sequestosome 1 (SQSTM1) serves as an adaptor of autophagy for degrading protein aggregates. The regulation of autophagy by EGFR and its clinical impacts are indicated in various types of cancer. However, the association of EGFR and SQSTM1 in OSCC is still unknown. Our results show that the expression levels of SQSTM1 and EGFR proteins are higher in tumor tissues than in the corresponding tumor-adjacent (CTAN) tissues of OSCC patients. The expression levels of SQSTM1 were positively associated with the EGFR expression level. High co-expression of SQSTM1 and EGFR is associated with poor prognosis in OSCC patients. Moreover, SQSTM1 expression is decreased in EGFR-knockdown cells. Cell growth and invasion/migration are also decreased in cells with single/combined knockdowns of EGFR and SQSTM1 or in SQSTM1-knockdown cells without EGFR kinase inhibitor Lapatinib treatment compared to that in scrambled cells. However, cell growth and invasion/metastasis were not significantly different between the scrambled cells and SQSTM1-knockdown cells in the presence of Lapatinib. This study is the first to indicate the biological roles and clinical significance of SQSTM1 regulation by EGFR in OSCC.
Highlights
Oral squamous cell carcinoma (OSCC), a subset of head and neck squamous cell carcinoma, accounts for over 90% of fatal oral cancers worldwide [1]
To compare protein expression levels of Epidermal growth factor receptor (EGFR) and Sequestosome 1 (SQSTM1) between corresponding tumor-adjacent normal tissues (CTAN) and tumor tissues in OSCC patients, EGFR and SQSTM1 expressions were analyzed by immunohistochemistry (IHC) staining
Protein expression levels of SQSTM1 were positively correlated with that of EGFR in tumor tissues of OSCC patients (r = 0.136, p < 0.001; Figure 1A). These results indicate that SQSTM1 and EGFR are highly expressed and positively correlated in tumor tissues of OSCC patients
Summary
Oral squamous cell carcinoma (OSCC), a subset of head and neck squamous cell carcinoma, accounts for over 90% of fatal oral cancers worldwide [1]. According to the National Comprehensive Cancer Network (NCCN, Plymouth Meeting, PA, USA) classification, the anatomic subsites of OSCC include buccal mucosa, tongue, mucosal lip, the gums, hard palate, retromolar trigone, alveolar ridge, and floor of the mouth [2]. SQSTM1 accumulation resulting from autophagy inhibition has been detected in several cancers and may contribute to tumor progression [10]. Epidermal growth factor receptor (EGFR), a member of the large family of growth factor receptors, acts as an oncogenic receptor tyrosine kinase [13]. It is strongly associated with cell proliferation and malignant tumor progression [14]. This study examines the biological roles of SQSTM1 regulation by EGFR in malignancy of OSCC cells and the clinical significance of EGFR/SQSTM1 co-expression in the prognosis of OSCC patients, which might provide a potential biomarker or therapeutic target for OSCC patients
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