Epigenetic Deregulation of Protein Tyrosine Kinase 6 Promotes Carcinogenesis of Oral Squamous Cell Carcinoma

Abstract

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underlying carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

Bioinformatics-based Investigation of Autophagy-Related Biomarkers in Heritable Ovarian Carcinoma

“…Studies have reported the potential of IL24 as a diagnostic marker in ovarian tumor subtypes, supporting its relevance in subtype-speci c diagnosis [17,18]. PTK6, also known as Protein Tyrosine Kinase 6, is another gene of interest that has been implicated in cancer pathogenesis [19][20][21]. Previous investigations have demonstrated the correlation between PTK6 expression and cancer stages in ovarian carcinoma, suggesting its potential as a staging biomarker for disease prognosis and management [22,23].…”

A New Molecular (P)Layer in Pseudomyxoma Peritonei: The Splicing Machinery is Dysregulated and Linked to Low Survival

“…Most importantly, analysis of the four genes using the REACTOME database associated their altered expression with key cancer-related molecular pathways. Namely, pathways related to PTK6 (Protein Tyrosine Kinase 6 or Brk), whose activity and regulation are strongly associated with multiple cancers, like colon [26] and breast cancer [32,33], oral squamous cell carcinoma [34] or hepatocellular carcinoma [35] by different mechanisms. Of note, one of these mechanisms relates to the appearance of a splicing isoform (Alt Brk) that may act by preventing tumor progression [32,33].…”

Utility of gamma‐glutamyl transpeptidase to lymphocyte count ratio in predicting prognosis of patients with oral cancer: A prospective cohort study in Southeastern China

“…1 It is the most prevalent type of head and neck cancer in the world. 2 The overall 5-year survival rate has not significantly increased over the previous decades despite continued therapeutic advances, making it as a serious global health problem. 3 It is essential to identify biomarkers that can precisely predict prognosis in order to provide more effective treatment.…”

“…Oral cancer is a general term for malignant tumors that form in different parts of the oral cavity and generally affect the tongue, floor of the mouth, gingiva, buccal mucosa, palate, and lips 1 . It is the most prevalent type of head and neck cancer in the world 2 . The overall 5‐year survival rate has not significantly increased over the previous decades despite continued therapeutic advances, making it as a serious global health problem 3 .…”