We show here that overexpression of the GOF mutant p53G245D and other GOF p53 mutants enhances the invasive cell growth of p53-deficient head and neck squamous cell carcinoma (HNSCC) UM-SCC-1 cells both in in vitro three-dimensional culture and in an in vivo orthotopic nude mouse model of HNSCC through a novel transcription-independent mechanism.
While HPV-negative tumors are characterized by tobacco-associated mutations in genes including TP53 and CDKN2A, in HPV-positive HNSCC integration of viral genome from HPV into the host cellular genome results in expression of the E6 and E7 viral oncoproteins, with consequent degradation of p53 and functional inactivation of Rb.
We used The Cancer Genome Atlas database to investigate the difference in transcriptome and proteome levels between mutated and wild-type TP53 HPV-negative HNSCC.
Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. circPVT1 up- and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines.
Overexpression of TP53 mutation-associated miR-182 may promote tumor cell proliferation and migration in HNSCC and suggest possible biomarker for the prediction of tumor recurrence.
TP53 mutations were determined in surgically resected primary tumor samples from six patients with high stage (II-IV), moderate to poorly differentiated head and neck squamous cell carcinoma (HNSCC).
Here, we reveal that ACTL6A, encoding an SWI/SNF subunit linked to stem cell and progenitor cell function, is frequently co-amplified and highly expressed together with the p53 family member p63 in head and neck squamous cell carcinoma (HNSCC).
The combination of vorinostat and AZD1775 inhibits tumor growth and angiogenesis <i>in vivo</i> in an orthotopic mouse model of oral cancer and prolongs animal survival.<b>Conclusions:</b> Vorinostat synergizes with AZD1775 in HNSCC cells with mutant p53 <i>in vitro</i> and <i>in vivo</i> A strategy combining HDAC and WEE1 inhibition deserves further clinical investigation in patients with advanced HNSCC.<i></i>.
Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients.
HNSCC early death was significantly associated with 3+ mutations (odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.16, 6.69), NOTCH1 mutations in non-Hispanic whites (OR = 5.51; 95% CI = 1.22-24.83) and TP53 mutations in Hispanic whites (OR = 3.84; 95% CI = 1.08-13.68) in multivariable analysis adjusted for age, sex, tumor site, and tumor stage.
We elucidated the interplay among mitogen-activated protein kinase (MAPK)-inhibition, radiation, and p53 mutations in vitro and in a novel ex vivo model derived from vital human HNSCC samples.
Older age, TP53 mutation, and HPV16 infection with oncogenic phenotypes were independently associated factors for HNSCC with odds ratios of 1.03 (1.02-1.05), 3.38 (1.71-6.66), and 9.19 (1.13-74.68), respectively.
Mechanistic studies reveal that attenuated HNSCC cell growth in response to DEK loss was associated with reduced expression of the oncogenic p53 family member, ΔNp63.
Human papillomavirus (HPV), p16 expression, and TP53 mutations are known prognostic factors in head and neck squamous cell carcinoma, but their role in squamous cell carcinoma of the anal canal (SCCAC) is less well established.
These results indicate that HNSCC cells expressing high-risk p53 mutations are significantly sensitized to cisplatin therapy by the selective wee-1 kinase inhibitor, supporting the clinical evaluation of MK-1775 in combination with cisplatin for the treatment of patients with TP53 mutant HNSCC.
TP53 is the most frequently altered gene in head and neck squamous cell carcinoma, with mutations occurring in over two-thirds of cases, but the prognostic significance of these mutations remains elusive.