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

Cancer Lett. 2017 Jan 28;385:21-27. doi: 10.1016/j.canlet.2016.11.002. Epub 2016 Nov 9.

Abstract

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.

Keywords: ATG10; Autophagy; EMT; Metastasis; PTBP1.

MeSH terms

  • Antigens, CD / metabolism
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Cadherins / metabolism
  • Cell Movement*
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Down-Regulation
  • Epithelial-Mesenchymal Transition
  • Gene Expression Regulation, Neoplastic
  • HCT116 Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism*
  • Humans
  • Hyaluronan Receptors / metabolism
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Polypyrimidine Tract-Binding Protein / genetics
  • Polypyrimidine Tract-Binding Protein / metabolism*
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Transfection
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

  • Antigens, CD
  • Autophagy-Related Proteins
  • CD44 protein, human
  • CDH1 protein, human
  • CDH2 protein, human
  • Cadherins
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Hyaluronan Receptors
  • PTBP1 protein, human
  • RNA, Messenger
  • Vesicular Transport Proteins
  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Polypyrimidine Tract-Binding Protein
  • ATG10 protein, human