Pin2/TRF1‑binding protein X1 inhibits colorectal cancer cell migration and invasion in vitro and metastasis in vivo via the nuclear factor‑κB signaling pathway

Oncol Rep. 2018 Sep;40(3):1533-1544. doi: 10.3892/or.2018.6570. Epub 2018 Jul 13.

Abstract

Pin2/TRF1‑binding protein X1 (PinX1) functioned as a potent inhibitor of telomerase, which was also widely considered to be a sufficient tumor suppressor. Previous studies have demonstrated that PinX1 expression was reduced in several types of cancer and was associated with poor overall survival. However, little is known regarding the role of PinX1 in colorectal cancer (CRC). The present study investigated PinX1 expression via immunostaining of CRC tissue microarrays consisting of tumor and adjacent non‑cancerous tissues (ANCT) from 568 patients. PinX1 expression was significantly lower in CRC tissues than in ANCT. Decreased PinX1 expression was revealed to be associated with lymph node metastasis, distant metastasis and advanced Tumor‑Node‑Metastasis stage, as well as a poorer overall and disease‑free survival. Furthermore, Cox regression analysis determined that a decreased PinX1 expression was an independent prognostic marker for patients with CRC. In an in vitro assay, PinX1 markedly restricted CRC cell migration and invasion. Additionally, the present study revealed that PinX1 could hinder the activity of matrix metalloproteinase 2 (MMP2) through nuclear factor (NF)‑κB‑dependent transcription to further suppress the migration and invasion ability of CRC cells through western blot analysis and a gelatin zymography assay. In vivo studies verified that PinX1 could suppress CRC metastasis, as well as the expression of MMP2 and NF‑κB p65. These results suggested that PinX1 can serve as an independent prognostic factor for patients with CRC and that it may function as a tumor metastasis suppressor in the progression of CRC though negatively regulating the NF‑κB/MMP2 signaling pathway.

Publication types

  • Retracted Publication

MeSH terms

  • Adenocarcinoma / metabolism
  • Adenocarcinoma / secondary*
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Cell Cycle Proteins
  • Cell Movement*
  • Cell Proliferation
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Colorectal Neoplasms / surgery
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • In Vitro Techniques
  • Lymphatic Metastasis
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Neoplasm Invasiveness
  • Prognosis
  • Signal Transduction
  • Survival Rate
  • Tumor Cells, Cultured
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Xenograft Model Antitumor Assays
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • NF-kappa B
  • PINX1 protein, human
  • Tumor Suppressor Proteins