A biosystems approach to identify the molecular signaling mechanisms of TMEM30A during tumor migration

PLoS One. 2017 Jun 22;12(6):e0179900. doi: 10.1371/journal.pone.0179900. eCollection 2017.

Abstract

Understanding the molecular mechanisms underlying cell migration, which plays an important role in tumor growth and progression, is critical for the development of novel tumor therapeutics. Overexpression of transmembrane protein 30A (TMEM30A) has been shown to initiate tumor cell migration, however, the molecular mechanisms through which this takes place have not yet been reported. Thus, we propose the integration of computational and experimental approaches by first predicting potential signaling networks regulated by TMEM30A using a) computational biology methods, b) our previous mass spectrometry results of the TMEM30A complex in mouse tissue, and c) a number of migration-related genes manually collected from the literature, and subsequently performing molecular biology experiments including the in vitro scratch assay and real-time quantitative polymerase chain reaction (qPCR) to validate the reliability of the predicted network. The results verify that the genes identified in the computational signaling network are indeed regulated by TMEM30A during cell migration, indicating the effectiveness of our proposed method and shedding light on the regulatory mechanisms underlying tumor migration, which facilitates the understanding of the molecular basis of tumor invasion.

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Cell Line, Tumor
  • Cell Movement*
  • Computational Biology / methods*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Signal Transduction*

Substances

  • ATP-Binding Cassette Transporters
  • Membrane Proteins
  • TMEM30a protein, human
  • ATP11A protein, human

Grants and funding

This work was sponsored by the National Natural Science Foundation of China (Grant Number 31500827), the Natural Science Foundation of Shanghai (Grant Number 14ZR1414400), and Young Eastern Scholar (Grant Number QD2015033). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.