The most common abnormalities downstream from EGFR in HNSCC are in the PI3K pathway, activated via loss of expression of the regulator PTEN, or via PI3K mutation.
Here we explore the impact of hypoxia on the behavior of HNSCC and define that the controlling function of phosphatase and tensin homolog (PTEN) over HIF-1α expression and CSC accumulation are de-regulated during hypoxic events.
The purpose of this study was to determine whether single nucleotide polymorphisms (SNPs) in AKT1, AKT2, FRAP1, PIK3CA, and PTEN were associated with treatment response and clinical outcome in patients with head and neck squamous cell carcinoma (HNSCC).
We hypothesize that the loss of PTEN expression as well as the subcellular localization could be of interest as a predictive marker of recurrence in HNSCC.
Overall, our study highlights the likely clinical relevance of reduced PTEN expression and/or inactivation in HNSCC progression, while the combined Pten deletion with exposure to tobacco carcinogens or their surrogates may provide a unique experimental model system to study novel molecular targeted treatments for HNSCC patients.
Mutations in the genes associated with the PI3K/AKT pathway including PI3K, AKT, RAS and PTEN, are infrequently found within head and neck squamous cell carcinoma and more specifically are rarely reported in oral squamous cell carcinoma (OSCC) cases.
To investigate the role of PTEN loss of expression in head and neck squamous cell carcinoma (HNSCC) response to cetuximab, we used siRNA in Cal 27 cells and then evaluated key signaling protein activation (pAKT and pERK 1/2) as well as cell viability and proliferation.
Activation of the PI3K/AKT/mTOR pathway downstream to kinase receptors, such as EGFR, was found in 57-81% of head and neck squamous cell carcinoma (HNSCC), and was eventually associated with a loss of PTEN function. mTOR was shown to modulate cell proliferation, apoptosis, invasion, and angiogenesis.
Our results suggest that nAChRs might exert their function through pathways different from PI3-K/Akt/PTEN and that alpha3, alpha5 or alpha7 nAChR subunit expression might not be useful prognostic markers in HNSCC.
We sequenced the entire coding region of the PTEN/MMAC1 gene in the remaining tumors displaying loss of heterozygosity and found one terminating mutation in a HNSCC sample.