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RNAscope for In situ Detection of Transcriptionally Active Human Papillomavirus in Head and Neck Squamous Cell Carcinoma
Published on: March 11, 2014
Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma
Shunsuke Kondo1, Hitoshi Hirakawa1, Taro Ikegami1
1Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara-cho, Okinawa, 903-0215, Japan.
Background:
Despite reports of a link between human papillomavirus (HPV) infection and mechanistic target of rapamycin (mTOR) signaling activation, the role of the mTOR pathway, especially raptor and rictor, in HPV-related head and neck cancer is still unclear. The aim of the present study was to elucidate the role of the mTOR pathway in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).
Methods:
The present study involved two strategies. The first was to investigate the activity of mTOR and mTOR-related complexes in high-risk HPV-positive (UM-SCC47 and CaSki) and HPV-negative (SCC-4 and SAS) cancer cell lines. The second was to elucidate mTOR complex expression in 80 oropharyngeal cancer tissues and to examine the relationship between mTOR complex expression and survival in patients with OPSCC.
Results:
The UM-SCC47 and CaSki cell lines showed high gene and protein expression of raptor. They also exhibited G1/S and G2/M phase cell cycle arrest following 24 h incubation with 6 μM temsirolimus, a rapamycin analog, and temsirolimus administration inhibited their growth. HPV-related OPSCC samples showed high gene and protein expression of raptor and rictor compared with HPV-unrelated OPSCC. In addition, HPV-related OPSCC patients with high raptor and rictor expression tended to have a worse prognosis than those with low or medium expression.
Conclusions:
These results suggest that raptor and rictor have important roles in HPV-related OPSCC and that temsirolimus is a potential therapeutic agent for patients with HPV-related OPSCC. This is the first report to reveal the overexpression of raptor and rictor in HPV-related OPSCC.
Insights
The mechanistic target of rapamycin (mTOR) pathway, specifically raptor and rictor, is overexpressed in human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). This suggests temsirolimus may be a potential treatment for HPV-related OPSCC.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Human papillomavirus (HPV) infection is linked to mechanistic target of rapamycin (mTOR) signaling.
- The specific role of mTOR pathway components, raptor and rictor, in HPV-related head and neck cancers remains unclear.
- This study investigates the mTOR pathway's role in HPV-related oropharyngeal squamous cell carcinoma (OPSCC).
Purpose of the Study:
- To elucidate the role of the mTOR pathway, including raptor and rictor, in HPV-related OPSCC.
- To assess the expression of mTOR complexes in HPV-related OPSCC tissues.
- To examine the relationship between mTOR complex expression and patient survival.
Main Methods:
- Investigated mTOR and related complex activity in HPV-positive and HPV-negative cancer cell lines.
- Analyzed mTOR complex expression in 80 oropharyngeal cancer tissue samples.
- Correlated mTOR complex expression with survival outcomes in OPSCC patients.
Main Results:
- High gene and protein expression of raptor was observed in HPV-positive cell lines.
- Temsirolimus (a rapamycin analog) induced cell cycle arrest and inhibited growth in HPV-positive cell lines.
- HPV-related OPSCC tissues showed higher raptor and rictor expression than HPV-unrelated OPSCC, correlating with worse prognosis.
Conclusions:
- Raptor and rictor play significant roles in HPV-related OPSCC.
- Temsirolimus demonstrates potential as a therapeutic agent for HPV-related OPSCC.
- This study is the first to report the overexpression of raptor and rictor in HPV-related OPSCC.
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