Polypyrimidine tract-binding protein 1-mediated down-regulation of ATG10 facilitates metastasis of colorectal cancer cells

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• 作者：Yoon Kyung Jo^a ; Seon Ae Roh^b ; Heejin Lee^c ; Na Yeon Park^a ; Eun Sun Choi^a ; Ju-Hee Oh^b ; So Jung Park^a ; Ji Hyun Shin^a ; Young-Ah Suh^b ; Eun Kyung Lee^c ; Dong-Hyung Cho^a ; ^{dhcho@khu.ac.kr} ; Jin Cheon Kim^b ; ^d ; ^{jckim@amc.seoul.kr}
• 关键词：ATG10 ; Autophagy ; PTBP1 ; Metastasis ; EMT
• 刊名：Cancer Letters
• 出版年：2017
• 出版时间：28 January 2017
• 年：2017
• 卷：385
• 期：Complete
• 页码：21-27
• 全文大小：1278 K
• 卷排序：385

文摘

Autophagy plays complex roles in tumor initiation and development, and the expression of autophagy-related genes (ATGs) is differentially regulated in various cancer cells, depending on their environment. In this study, we analyzed the expressional relationship between polypyrimidine tract-binding protein 1 (PTBP1) and ATG10 in metastatic colorectal cancer. PTBP1 is associated with tumor metastasis in primary colorectal tumors and colorectal cancer liver metastasis (CLM) tissues. In addition, PTPB1 directly interacts with mRNA of ATG10, and regulates ATG10 expression level in colorectal cancer cells. Ectopic expression of PTBP1 decreased ATG10 expression, whereas down-regulation of PTBP1 increased ATG10 level. In contrast to PTBP1, expression of ATG10 was decreased in CLM tissues. Knock down of ATG10 promoted cell migration and invasion of colorectal cancer cells. Moreover, depletion of ATG10 modulated epithelial-mesenchymal transition-associated proteins in colorectal cancer cells: N-cadherin, TCF-8/ZEB1, and CD44 were up-regulated, whereas E-cadherin was down-regulated. Taken together, our findings suggest that expression of ATG10 negatively regulated by PTBP1 is associated with metastasis of colorectal cancer cells.