Deregulated Expression of SRC, LYN and CKB Kinases by DNA Methylation and Its Potential Role in Gastric Cancer Invasiveness and Metastasis

Abstract

Kinases are downstream modulators and effectors of several cellular signaling cascades and play key roles in the development of neoplastic disease. In this study, we aimed to evaluate SRC, LYN and CKB protein and mRNA expression, as well as their promoter methylation, in gastric cancer. We found elevated expression of SRC and LYN kinase mRNA and protein but decreased levels of CKB kinase, alterations that may have a role in the invasiveness and metastasis of gastric tumors. Expression of the three studied kinases was also associated with MYC oncogene expression, a possible biomarker for gastric cancer. To understand the mechanisms that regulate the expression of these genes, we evaluated the DNA promoter methylation of the three kinases. We found that reduced SRC and LYN methylation and increased CKB methylation was associated with gastric cancer. The reduced SRC and LYN methylation was associated with increased levels of mRNA and protein expression, suggesting that DNA methylation is involved in regulating the expression of these kinases. Conversely, reduced CKB methylation was observed in samples with reduced mRNA and protein expression, suggesting CKB expression was found to be only partly regulated by DNA methylation. Additionally, we found that alterations in the DNA methylation pattern of the three studied kinases were also associated with the gastric cancer onset, advanced gastric cancer, deeper tumor invasion and the presence of metastasis. Therefore, SRC, LYN and CKB expression or DNA methylation could be useful markers for predicting tumor progression and targeting in anti-cancer strategies.

miR‐1 suppresses the proliferation and promotes the apoptosis of esophageal carcinoma cells by targeting Src

“…In addition to frequent straggly phosphorylation, abnormal expressions of Src protein were also seen in neoplastic diseases. Elevated expression of Src protein was found to be related to invasiveness and metastasis in gastric tumors . Studies also asserted that overexpression of Src was observed in high‐grade leiomyosarcoma, making Src a potential valuable diagnostic marker for this soft tissue sarcoma .…”

Genome-wide transcriptional analysis of Aristolochia manshuriensis induced gastric carcinoma

“…Hras was up-regulated in rats with gastric precancerous lesions (Shen et al 2008). Myc as a possible biomarker for GC, the mRNA expression, protein expression, as well as gene copy numbers were evaluated in human GC samples (De Souza et al 2013;Mello et al 2015). SRC, a cell cycle regulator and transcriptional factor, was up-regulated in human GC samples (Mello et al 2015).…”

“…Myc as a possible biomarker for GC, the mRNA expression, protein expression, as well as gene copy numbers were evaluated in human GC samples (De Souza et al 2013;Mello et al 2015). SRC, a cell cycle regulator and transcriptional factor, was up-regulated in human GC samples (Mello et al 2015). Gnai3 was significantly associated with gastric cardia cancer risk (Li et al 2013).…”

Identification of metabolism-associated genes and construction of a prognostic signature in bladder cancer

“…Yamada Y et al revealed that overexpression of PLOD1 was closely related to poor survival and downregulation of PLOD1 can decrease the progression of BC [40]. CKB was participated in metabolic processes involving glycolysis and could serve as a biomarker for predicting tumor progression [41]. However, the precise role of CKB in the occurrence and progression of BC has not been well studied.…”