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Expression of the double‐stranded RNA‐dependent kinase PKR influences osteosarcoma attachment independent growth, migration, and invasion
Author(s) -
Piazzi Manuela,
Bavelloni Alberto,
Greco Sara,
Focaccia Enrico,
Orsini Arianna,
Benini Stefania,
Gambarotti Marco,
Faenza Irene,
Blalock William L.
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29024
Subject(s) - protein kinase r , osteosarcoma , rna , kinase , microbiology and biotechnology , eif 2 kinase , protein kinase a , cancer research , chemistry , biology , mitogen activated protein kinase kinase , cyclin dependent kinase 2 , genetics , gene
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.