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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 9243-9250 |
| Number of pages | 8 |
| Journal | Oncotarget |
| Volume | 8 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2017 |
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Keywords
- Immunohistochemistry
- Phosphorylation
- Replication protein A
- Squamous cell carcinoma
- Tumorigenicity
ASJC Scopus subject areas
- Oncology
Cite this
S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas. / 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.; Oakley, Gregory G.
In: Oncotarget, Vol. 8, No. 6, 01.01.2017, p. 9243-9250.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - S4S8-RPA phosphorylation as an indicator of cancer progression in oral squamous cell carcinomas
AU - Rector, Jeff
AU - Kapil, Sasha
AU - Treude, Kelly J.
AU - Kumm, Phyllis
AU - Glanzer, Jason G.
AU - Byrne, Brendan M.
AU - Liu, Shengqin
AU - Smith, Lynette M
AU - DiMaio, Dominick J
AU - Giannini, Peter J
AU - Smith, Russell B.
AU - Oakley, Gregory G
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Immunohistochemistry
KW - Phosphorylation
KW - Replication protein A
KW - Squamous cell carcinoma
KW - Tumorigenicity
UR - http://www.scopus.com/inward/record.url?scp=85011964393&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85011964393&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.14001
DO - 10.18632/oncotarget.14001
M3 - Article
C2 - 27999209
AN - SCOPUS:85011964393
VL - 8
SP - 9243
EP - 9250
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 6
ER -