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A novel role mediated by adenoviral E1A in suppressing cancer through modulating decorin.

Yan GeWen ZhangJing QinChen ZhangWeiping TianQi ZhangJie ShaoShasha LiLin FangJunnian Zheng
Published in: Medical oncology (Northwood, London, England) (2019)
Oncolytic adenovirus is an emerging alternative to current therapeutics. The adenoviral E1A, the first protein expressed upon oncolytic adenoviral infection, has been identified as an antitumor agent, but the mechanisms of its tumor inhibition ability are unclear enough. Decorin is ubiquitous in the extracellular matrix (ECM), which regulates multiple functions through interaction with ECM. Here, we intended to explore the effects of adenoviral E1A on the tumor extracellular matrix during gene therapy. We demonstrated that reduced decorin expression was found in patients with lung cancer. The adenoviral E1A or a mutant adenoviral E1A with Rb-binding ability absent (E1A 30-60aa, 120-127aa deletion) could increase the expression of decorin and down-regulate VEGF, two members of tumor ECM, involved in both vasculogenesis and angiogenesis. E1A/mE1A-mediated suppressing the migration and invasion ability of tumor cells was depended on decorin. E1A interacted with decorin directly and induced the proteasomal degradation of VEGF. In addition, E1A or mE1A can inhibit tumor growth in a subcutaneous lung cancer xenograft model. It suggested that decorin might be a crucial mediator among ECM components for adenoviral E1A-mediated antitumor activities. These studies on adenovirus E1A provide a new mechanism for the emerging therapies of tumor gene therapy.
Keyphrases
  • extracellular matrix
  • gene therapy
  • vascular endothelial growth factor
  • endothelial cells
  • poor prognosis
  • signaling pathway
  • small molecule
  • young adults
  • protein protein
  • long non coding rna