PTBP1 promotes the growth of breast cancer cells through the PTEN/Akt pathway and autophagy

J Cell Physiol. 2018 Nov;233(11):8930-8939. doi: 10.1002/jcp.26823. Epub 2018 Jun 1.

Abstract

Invasion and migration is the hallmark of malignant tumors as well as the major cause for breast cancer death. The polypyrimidine tract binding, PTB, protein serves as an important model for understanding how RNA binding proteins affect proliferation and invasion and how changes in the expression of these proteins can control complex programs of tumorigenesis. We have investigated some roles of polypyrimidine tract binding protein 1 (PTBP1) in human breast cancer. We found that PTBP1 was upregulated in breast cancer tissues compared with normal tissues and the same result was confirmed in breast cancer cell lines. Knockdown of PTBP1 substantially inhibited tumor cell growth, migration, and invasion. These results suggest that PTBP1 is associated with breast tumorigenesis and appears to be required for tumor cell growth and maintenance of metastasis. We further analyzed the relationship between PTBP1 and clinicopathological parameters and found that PTBP1 was correlated with her-2 expression, lymph node metastasis, and pathological stage. This will be a novel target for her-2(+ ) breast cancer. PTBP1 exerts these effects, in part, by regulating the phosphatase and tensin homolog-phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PTEN-PI3K/Akt) pathway and autophagy, and consequently alters cell growth and contributes to the invasion and metastasis.

Keywords: PTEN/Akt signal pathway; autophagy; breast cancer; polypyrimidine tract binding protein 1 (PTBP1).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy / genetics*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterogeneous-Nuclear Ribonucleoproteins / genetics*
  • Humans
  • Lymphatic Metastasis / genetics
  • Lymphatic Metastasis / pathology
  • MCF-7 Cells
  • Mice
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Metastasis
  • Oncogene Protein v-akt / genetics
  • PTEN Phosphohydrolase / genetics
  • Polypyrimidine Tract-Binding Protein / genetics*
  • RNA-Binding Proteins / genetics*
  • Receptor, ErbB-2 / genetics
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays

Substances

  • Heterogeneous-Nuclear Ribonucleoproteins
  • PTBP1 protein, human
  • RNA-Binding Proteins
  • Polypyrimidine Tract-Binding Protein
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Oncogene Protein v-akt
  • PTEN Phosphohydrolase