Effect of EGFR on SQSTM1 Expression in Malignancy and Tumor Progression of Oral Squamous Cell Carcinoma

• Published in: International journal of molecular sciences Vol. 22; no. 22; p. 12226
• Main Authors: Tseng, Yu-Kai, Chen, Chun-Feng, Shu, Chih-Wen, Lee, Cheng-Hsin, Chou, Yan-Ting, Li, Yi-Jing, Liou, Huei-Han, Cheng, Jiin-Tsuey, Chen, Chun-Lin, Ger, Luo-Ping, Liu, Pei-Feng
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.11.2021; MDPI
• Subjects: Autophagy; Biomarkers; Cancer therapies; Cell growth; Cell Line, Tumor; Chemotherapy; Enzyme inhibitors; epidermal growth factor receptor; Epidermal growth factor receptors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Female; Gene Expression Regulation, Neoplastic; Growth factors; Humans; Kinases; Lymphatic system; Male; Malignancy; Medical prognosis; Metastases; Metastasis; Middle Aged; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; Oral cancer; Oral carcinoma; Oral squamous cell carcinoma; Patients; Phagocytosis; prognosis; Protein expression; Proteins; Roles; sequestosome 1; Sequestosome-1 Protein - genetics; Squamous cell carcinoma; Squamous Cell Carcinoma of Head and Neck - genetics; Squamous Cell Carcinoma of Head and Neck - metabolism; Tongue; Tumorigenesis; Tumors; oral squamous cell carcinoma; malignancy; prognosis; epidermal growth factor receptor; sequestosome 1
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222212226

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.