Inhibition of cell-adhesion protein DPYSL3 promotes metastasis of lung cancer

Respir Res. 2018 Mar 7;19(1):41. doi: 10.1186/s12931-018-0740-0.

Abstract

Background: Our previous screening study suggested that the cell-adhesions protein Dihydropyrimidinase-like 3 (DPYSL3) was a candidate metastatic lung cancer related molecule. This study aimed to analyze the correlation between DPYSL3 and metastatic lung cancer.

Methods: Stable DPYSL3 knockdown Lewis lung carcinoma (LLC) cells were constructed with a retroviral system. Cell migration and invasion assays were performed to determine the role of DPYSL3 in LLC cells' migration and invasion changes. A metastatic lung tumor model in which the stable DPYSL3 knockdown LLC cells were injected through tail vein was used to analyze the role of DPYSL3 in tumor metastasis in vivo. The correlation between DPYSL3 expression and the survival time of lung cancer patients were analyzed in KMPLOT database.

Results: Knockdown of DPYSL3 promoted the migratory and invasive of LLC cells compared to the control group. Meanwhile, the motility of LLC cells was also increased with the inhibition of DPYSL3. The TGFβ-induced EMT increased when DPYSL3 was inhibited. The expression of EMT markers, TWIST1 and N-cadherin, significantly increased to almost two times with the knockdown of DPYSL3. Furthermore, inhibition of DPYSL3 promoted the progression of metastatic xenograft in C57BL/6 mice. The expression level of DPYSL3 decreased in lung cancer patients with distant metastasis.

Conclusions: Knockdown of DPYSL3 promoted the metastatic ability of LLC cells in vitro and in vivo.

Keywords: DPYSL3; EMT; LLC cells; Lung cancer; Metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / metabolism*
  • Carcinoma, Lewis Lung / pathology*
  • Cell Adhesion Molecules / antagonists & inhibitors*
  • Cell Adhesion Molecules / deficiency*
  • Cell Movement / physiology
  • Gene Knockdown Techniques / methods
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Nude
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / deficiency*
  • Xenograft Model Antitumor Assays / methods

Substances

  • Cell Adhesion Molecules
  • Crmp-4 protein, mouse
  • Nerve Tissue Proteins