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

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.

Novel ferroptosis signature for improving prediction of prognosis and indicating gene targets from single-cell level in oral squamous cell carcinoma

“…Zhang et al elucidated that EGFR regulates the sensitivity of OSCC cells to JQ1 (an antitumor agent) through a signaling pathway [ 28 ]. In addition, another study showed that EGFR modulates the malignant mechanisms of OSCC by regulating sequestosome-1, an autophagy-related protein [ 29 ].…”

“…CA9, CAV1, AURKA, and EGFR are the hub genes of the 10-FRDEGs model and are markers and molecular targets of poor prognosis in patients with OSCC. So far, some progress has been achieved in the investigation of the regulatory roles of AURKA and EGFR in OSCC [ 27 , 29 ].However, CA9 and CAV1 are only linked with the susceptibility and prognosis of patients with OSCC [ 45 , 46 ]. In this study, to identify novel molecular therapeutic targets for OSCC based on the 10-FRDEGs risk scoring model in OSCC, we investigated the RNA and protein expression levels and molecular functions of CA9 and CAV1.…”

HCRP‑1 alleviates the malignant phenotype and angiogenesis of oral squamous cell carcinoma cells via the downregulation of the EGFR/STAT3 signaling pathway

“…Subsequently, it was demonstrated that HCRP-1 overexpression inhibited EGFR phosphorylation and that EGF treatment markedly increased EGFR expression in cells, which reversed the effects of HCRP-1 overexpression. EGFR signaling is involved in the malignant process of OSCC ( 40 ) and it can therefore be hypothesized that HCRP-1 can alleviate the malignant phenotype of cells via the inhibition of EGFR.…”

TMEM211 Promotes Tumor Progression and Metastasis in Colon Cancer

“…The migration distance of the cells was observed and quantified. The detailed protocol was described in a previous report [ 40 ].…”