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Updated: Jul 9, 2026
A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
Published on: January 5, 2017
Oncogenic mutations of the PIK3CA gene in head and neck squamous cell carcinomas
Avaniyapuram Kannan Murugan1, Nguyen Thi Hong, Yasuhisa Fukui
1Department of Molecular Cellular Oncology and Microbiology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan.
Abstract:
Phosphatidylinositol 3-kinases (PI3Ks) are heterodimeric lipid kinases that regulate cellular activities such as proliferation, survival, motility and morphology. Recent studies reported that the p110alpha (PIK3CA), catalytic subunit of PI3-kinase is somatically mutated in human cancers. Hot- spot mutations (E542K, E545K and H1047R) are reported to have higher oncogenic potential. Although PIK3CA mutations were reported in head and neck squamous cell carcinomas (HNSCC) of limited ethnicity, the functional consequences of HNSCC-associated PIK3CA mutations have not been examined. Status of PI3K signaling related genes (PTEN-RAS-EGFR) in the presence of PIK3CA mutation have not been reported. In this study, we analyzed exons 9 and 20 of PIK3CA in 54 samples, including 17 HNSCC cell lines, 19 Indian and 18 Vietnamese primary tumors. We found mutations in 29.4% (5/17) of HNSCC cell lines, 10.5% (2/19) of Indian tumors and no mutation (0/18) in Vietnamese tumors. Two homozygous PIK3CA mutations were found in cell lines and a novel insertion mutation with oncogenicity in Indian tumor. Analysis of PI3K signaling related genes showed that PIK3CA and PTEN mutations were mutually exclusive, though PTEN mutation is uncommon in HNSCC. However, PIK3CA mutation coexisted with H-RAS mutation. Furthermore, PIK3CA mutations were mutually exclusive to EGFR amplification. All the 5 mutants that we found in HNSCC, showed increased PI3 kinase activities, followed by growth factor independent higher colony forming efficiency, changes in morphology, higher rates of migration and invasion compared with PIK3CA wild-type. Our study is the first to examine the oncogenic potential of PIK3CA mutants associated with HNSCC and report on PIK3CA mutations in Indian and Vietnamese ethnicity. These results suggest that PIK3CA mutations in HNSCC are likely to be oncogenic and may significantly contribute to HNSCC carcinogenesis and pave attractive target for therapeutic prevention.
Insights
Mutations in PIK3CA, a key gene in head and neck cancers, enhance cell growth and invasion. This study reveals PIK3CA mutations in Indian HNSCC, offering potential therapeutic targets.
Area of Science:
- Molecular Oncology
- Cancer Genomics
- Cell Signaling Pathways
Background:
- Phosphatidylinositol 3-kinases (PI3Ks) regulate critical cellular functions.
- The catalytic subunit PIK3CA is frequently mutated in various cancers.
- PIK3CA mutations in head and neck squamous cell carcinomas (HNSCC) and their functional impact remain underexplored, especially across diverse ethnicities.
Purpose of the Study:
- To investigate the prevalence and functional consequences of PIK3CA mutations in HNSCC.
- To analyze the co-occurrence of PIK3CA mutations with other key signaling genes (PTEN, RAS, EGFR).
- To assess the oncogenic potential of HNSCC-associated PIK3CA mutants.
Main Methods:
- Exon sequencing of PIK3CA in 54 HNSCC samples (cell lines, Indian, and Vietnamese tumors).
- Analysis of PI3K signaling pathway genes (PTEN, RAS, EGFR).
- Functional assays evaluating PI3 kinase activity, colony formation, morphology, migration, and invasion.
Main Results:
- PIK3CA mutations were identified in 29.4% of cell lines and 10.5% of Indian tumors, but not in Vietnamese tumors.
- PIK3CA and PTEN mutations were mutually exclusive; PIK3CA mutations coexisted with H-RAS mutations and were mutually exclusive to EGFR amplification.
- All identified PIK3CA mutants exhibited increased PI3 kinase activity, enhanced growth factor-independent proliferation, altered morphology, and increased migration/invasion.
Conclusions:
- PIK3CA mutations are oncogenic drivers in HNSCC, contributing to cancer development.
- This study provides the first functional analysis of PIK3CA mutants in HNSCC and reports mutations in Indian and Vietnamese populations.
- Targeting PIK3CA mutations represents a promising therapeutic strategy for HNSCC.
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