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Updated: Jan 23, 2026

Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
Published on: March 5, 2019
Expression of the double-stranded RNA-dependent kinase PKR influences osteosarcoma attachment independent growth,
Manuela Piazzi1,2, Alberto Bavelloni2, Sara Greco3
1Istituto di Genetica Molecolare-Luigi Luca Cavalli Sforza, UOS Bologna, Consiglio Nazionale Delle Ricerche (IGM-CNR), Bologna, Italy.
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.
Insights
This study reveals that double-stranded RNA-dependent protein kinase (PKR), a key inflammatory signaling molecule, promotes osteosarcoma (OS) growth and metastasis. PKR activation may serve as a prognostic indicator for this rare bone cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Osteosarcoma (OS) is a rare bone cancer primarily affecting young individuals.
- Lung metastasis of OS is the main cause of mortality.
- Innate immune and inflammatory signaling pathways in OS development are understudied.
Purpose of the Study:
- To investigate the role of double-stranded RNA-dependent protein kinase (PKR) in osteosarcoma (OS) progression.
- To determine if PKR influences OS cell growth, migration, and invasion.
- To explore the potential prognostic value of PKR in OS.
Main Methods:
- Stable transfection of U2OS and SaOS-2 osteosarcoma cell lines with wild-type or dominant-negative (DN) PKR.
- Assessment of anchorage-independent growth (soft agar colony formation).
- Evaluation of cell migration and invasion capabilities.
Main Results:
- Overexpression of PKR significantly enhanced colony formation, migration, and invasion in OS cells.
- Conversely, dominant-negative PKR inhibited attachment-independent growth, migration, and invasion.
- These findings highlight PKR's pro-tumorigenic role in osteosarcoma.
Conclusions:
- Inflammatory signaling, mediated by PKR, plays a significant role in osteosarcoma initiation and metastasis.
- PKR expression and activation status may hold prognostic value for osteosarcoma patients.
- Targeting PKR could represent a novel therapeutic strategy for osteosarcoma.
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