Zyxin inhibits the epithelial–mesenchymal transition process in gastric cancer by upregulating SIRT1
Jing Lou,
Sha Geng,
Wei He,
Song‐Bai Liu,
Xinghong Shi,
Ying Chang,
Shiyuan Han,
Panting Qian,
Hesham M Amin,
Yao‐Hua Song,
Yangxin Li,
Jin Zhou
Affiliations
Jing Lou
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Sha Geng
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Wei He
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Song‐Bai Liu
Suzhou Key Laboratory of Medical Biotechnology Suzhou Vocational Health College Suzhou China
Xinghong Shi
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Ying Chang
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Shiyuan Han
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Panting Qian
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Hesham M Amin
Department of Hematopathology The University of Texas MD Anderson Cancer Center Houston Texas USA
Yao‐Hua Song
Cyrus Tang Hematology Center Collaborative Innovation Center of Hematology Soochow University Suzhou China
Yangxin Li
Institute for Cardiovascular Science and Department of Cardiovascular Surgery First Affiliated Hospital and Medical College of Soochow University Collaborative Innovation Center of Hematology Soochow University Suzhou Jiangsu China
Jin Zhou
Department of General Surgery the First Affiliated Hospital of Soochow University Suzhou China
Abstract Tumor development relies on the stemness of cancer stem cells, which is regulated by environmental cues. Previous studies have shown that zyxin can inhibit the expression of genes for embryonic stem cell status. In the present study, the expression levels of zyxin protein in cancer tissues and adjacent noncancerous tissues from 73 gastric cancer patients with different clinical stages were analyzed by Western blot. We showed that the relative expression levels of zyxin in gastric cancer tissues (cancer tissues/adjacent tissues) were significantly downregulated in advanced clinical stages. Overexpression of zyxin inhibited the stemness and epithelial–mesenchymal transition (EMT) processes in gastric cancer cells. Zyxin also inhibited the proliferation, migration, and invasion but increased the sensitivity of cancer cells to drugs. Overexpression of zyxin in MKN45 cells inhibited tumor growth in nude mice. We show that the interactions between zyxin and SIRT1 led to the upregulation of SIRT1, reduced acetylation levels of histone H3 K9 and K23, decreased transcription levels of SNAI 1/2, and inhibition of the EMT process. This study demonstrated that zyxin negatively regulates the progression of gastric cancer by inhibiting the stemness of cancer stem cells and EMT. Our findings shed new light on the pathogenesis of gastric cancer.
