Obg-like ATPase 1 inhibited oral carcinoma cell metastasis through TGFβ/SMAD2 axis in vitro

BMC Mol Cell Biol. 2020 Sep 14;21(1):65. doi: 10.1186/s12860-020-00311-z.

Abstract

Background: The human Obg-like ATPase 1 (OLA1) protein has been reported to play an important role in cancer cell proliferation. The molecular mechanism underlying OLA1 regulated oral metastasis is still unknown. We investigated in this study the regulatory role of OLA1 playing in oral squamous cell metastasis.

Results: A series of in vitro assays were performed in the cells with RNAi-mediated knockdown or overexpression to expound the regulatory function of OLA1 in oral cancer. We found that the endogenous level of OLA1 in a highly metastatic oral squamous cell line was significantly lower than that in low metastatic oral cells as well as in normal oral cells. Escalated expression of OLA1 resulted in a reduced ability of metastasis in highly metastatic cells, and enhanced its sensitivity to the paclitaxel treatment. Further analysis of the EMT markers showed that Snail, Slug, N-cadherin were up-expressed significantly. Meanwhile, E-cadherin was significantly down-regulated in the oral cancer cells with OLA1-knocked down, suggesting that OLA1 inactivated EMT process. Furthermore, we found that OLA1 suppressed oral squamous cell metastasis by suppressing the activity of a TGFβ/SMAD2/EMT pathway.

Conclusion: Our data suggests that OLA1 may be developed as a potential target for the treatment of oral cancer metastasis.

Keywords: EMT; Metastasis; OLA1; Oral squamous cell carcinoma; SMAD2.

MeSH terms

  • Adenosine Triphosphatases / metabolism*
  • Cadherins / metabolism
  • Carcinoma / drug therapy
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Mouth Neoplasms / drug therapy
  • Mouth Neoplasms / metabolism*
  • Mouth Neoplasms / pathology
  • Neoplasm Metastasis / drug therapy
  • Neoplasm Metastasis / pathology*
  • Paclitaxel / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Smad2 Protein / metabolism*
  • Snail Family Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • Cadherins
  • SMAD2 protein, human
  • Smad2 Protein
  • Snail Family Transcription Factors
  • Transforming Growth Factor beta
  • Adenosine Triphosphatases
  • GTP-Binding Proteins
  • OLA1 protein, human
  • Paclitaxel