Expression of the double-stranded RNA-dependent kinase PKR influences osteosarcoma attachment independent growth, migration, and invasion

Manuela Piazzi, Alberto Bavelloni, Sara Greco, Enrico Focaccia, Arianna Orsini, Stefania Benini, Marco Gambarotti, Irene Faenza, William L Blalock

Research output: Contribution to journalArticle

Abstract

Osteosarcoma (OS) is a rare, insidious tumor of mesenchymal origin that most often affects children, adolescents, and young adults. While the primary tumor can be controlled with chemotherapy and surgery, it is the lung metastases that are eventually fatal. Multiple studies into the initial drivers of OS development have been undertaken, but few of these have examined innate immune/inflammatory signaling. A central figure in inflammatory signaling is the innate immune/stress-activated kinase double-stranded RNA-dependent protein kinase (PKR). To characterize the role of PKR in OS, U2OS, and SaOS-2 osteosarcoma cell lines were stably transfected with wild-type or dominant-negative (DN) PKR. Overexpression of PKR enhanced colony formation in soft agar (U2OS and SaOS-2), enhanced cellular migration (U2OS), and invasive migration (SaOS-2). In contrast, overexpression of DN-PKR inhibited attachment-independent growth, migration and/or invasion. These data demonstrate a role for inflammatory signaling in OS formation and migration/invasion and suggest the status of PKR expression/activation may have prognostic value.

Original languageEnglish
Pages (from-to)1103-1119
Number of pages17
JournalJournal of Cellular Physiology
Volume235
Issue number2
DOIs
Publication statusE-pub ahead of print - Jun 25 2019

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Keywords

  • inflammation
  • innate immunity
  • metastases
  • osteosarcoma
  • signal transduction

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