S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas.

Authors

Jeff Rector, University of Nebraska Medical Center
Sasha Kapil, University of Nebraska Medical Center
Kelly J. Treude, University of Nebraska Medical Center
Phyllis Kumm, University of Nebraska Medical CenterFollow
Jason G. Glanzer, University of Nebraska Medical Center
Brendan M. Byrne, University of Nebraska Medical Center
Shengqin Liu, University of Nebraska Medical Center
Lynette M. Smith, University of Nebraska-LincolnFollow
Dominick J. DiMaio, University of Nebraska Medical CenterFollow
Peter J. Giannini, University of Nebraska Medical CenterFollow
Russell B. Smith, University of Nebraska Medical Center
Greg G. Oakley, University of Nebraska Medical CenterFollow

Document Type

Article

Journal Title

Oncotarget

Publication Date

Winter 2-7-2017

Volume

8

Abstract

Oral cancers are easily accessible compared to many other cancers. Nevertheless, oral cancer is often diagnosed late, resulting in a poor prognosis. Most oral cancers are squamous cell carcinomas that predominantly develop from cell hyperplasias and dysplasias. DNA damage is induced in these tissues directly or indirectly in response to oncogene-induced deregulation of cellular proliferation. Consequently, a DNA Damage response (DDR) and a cell cycle checkpoint is activated. As dysplasia transitions to cancer, proteins involved in DNA damage and checkpoint signaling are mutated or silenced decreasing cell death while increasing genomic instability and allowing continued tumor progression. Hyperphosphorylation of Replication Protein A (RPA), including phosphorylation of Ser4 and Ser8 of RPA2, is a well-known indicator of DNA damage and checkpoint activation. In this study, we utilize S4S8-RPA phosphorylation as a marker for cancer development and progression in oral squamous cell carcinomas (OSCC). S4S8-RPA phosphorylation was observed to be low in normal cells, high in dysplasias, moderate in early grade tumors, and low in late stage tumors, essentially supporting the model of the DDR as an early barrier to tumorigenesis in certain types of cancers. In contrast, overall RPA expression was not correlative to DDR activation or tumor progression. Utilizing S4S8-RPA phosphorylation to indicate competent DDR activation in the future may have clinical significance in OSCC treatment decisions, by predicting the susceptibility of cancer cells to first-line platinum-based therapies for locally advanced, metastatic and recurrent OSCC.

DOI Link

10.18632/oncotarget.14001

ISSN

1949-2553

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.

Recommended Citation

Rector, Jeff; Kapil, Sasha; Treude, Kelly J.; Kumm, Phyllis; Glanzer, Jason G.; Byrne, Brendan M.; Liu, Shengqin; Smith, Lynette M.; DiMaio, Dominick J.; Giannini, Peter J.; Smith, Russell B.; and Oakley, Greg G., "S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas." (2017). Journal Articles: College of Dentistry. 27.
https://digitalcommons.unmc.edu/cod_articles/27