Expression and significance of Caspase-3 and Caspase-6 in gastric cancer

Posted by Lisa Clara on November 15th, 2019

Gastric cancer is one of the most common digestive tract tumors in China, accounting for the first place in the mortality rate of malignant tumors, which seriously endangers human health. The occurrence and development of gastric cancer is the result of multiple factors and multiple genes. The imbalance between apoptosis and cell proliferation plays an important role in the development of gastric cancer. The Caspase family is a family of cysteine proteases that play an important role in the process of apoptosis and determine the morphological and biochemical changes in apoptosis. At present, there are 14 members of the family, named Caspase-1-Caspase-14, among which Caspase-3 and Caspase-6 are important effectors in the Caspase family. Caspase-3 and Caspase-6 proteins can be further activated after the initial Caspases protein is activated. It is noteworthy that Caspase-3 and Caspase-6 genes are closely related, located at 4q34 and 4q25, respectively, with 38% homology, and both are synthesized in the cytoplasm as zymogen, which are major apoptotic effectors.

T. Hoshi et al. found that the decrease of Caspase-3 protein expression in gastric cancer tissues inhibited the apoptosis of gastric cancer cells, indicating that it may be involved in the formation and evolution of gastric cancer. Qi Wanxin et al found that the expression of Caspase-3 protein in gastric cancer decreased significantly, and its expression decreased with the decrease of tissue differentiation, but the expression of Caspase-3 protein was not a prognostic factor for gastric cancer. As part of a feedback loop, the Caspase-6 gene plays an important role in promoting apoptosis induced by bile acids. During apoptosis, Caspase-6 cleaves the lamellar protein, causing the laminar layer to disintegrate, which in turn leads to chromosome agglutination. Caspase-6 protein is expressed in different degrees in normal heart, spleen, liver, kidney and other tissues. Renal tissue is mainly expressed in renal tubular epithelial cells, and glomeruli are not expressed.

JWLee et al. used immunohistochemistry to study the expression rate of Caspase-6 protein in colorectal cancer and gastric cancer. The results were 90% and 60%, respectively. There was no significant difference in the expression rate of normal tissues between colorectal cancer and normal tissues. The low expression rate in gastric cancer suggests that it may be related to the pathogenesis of gastric cancer. The role of the Caspase family of proteins is to promote apoptosis, and cancer cells show a trend of near-infinite growth, which is related to the inactivation or attenuation of apoptosis.

Rao et al. found that Caspase-3 and Caspase-6 genes were significantly higher in normal tissues adjacent to cancer than in gastric cancer tissues. The earlier the tumor infiltration depth, the higher the degree of differentiation, indicating that the closer the tumor tissue is to the normal tissue, the smaller the atypicality, the higher the expression rate of Caspase-3 gene and Caspase-6 gene.

In conclusion, further study on the mechanism of loss or low expression of Caspase-3 and Caspase-6 genes in gastric cancer tissues, targeting their expression in gastric cancer tissues, activating apoptosis mechanism, and promoting apoptosis of cancer cells, not only for gastric cancer The pathogenesis and treatment are of great significance and may provide new avenues for the treatment of other malignant tumors.