Cancers, Vol. 11, Pages 1347: The miR-205-5p/BRCA1/RAD17 Axis Promotes Genomic Instability in Head and Neck Squamous Cell Carcinomas

Cancers, Vol. 11, Pages 1347: The miR-205-5p/BRCA1/RAD17 Axis Promotes Genomic Instability in Head and Neck Squamous Cell Carcinomas Cancers doi: 10.3390/cancers11091347 Authors: Valenti Sacconi Ganci Grasso Strano Blandino Agostino Defective DNA damage response (DDR) is frequently associated with tumorigenesis. Abrogation of DDR leads to genomic instability, which is one of the most common characteristics of human cancers. TP53 mutations with gain-of-function activity are associated with tumors under high replicative stress, high genomic instability, and reduced patient survival. The BRCA1 and RAD17 genes encode two pivotal DNA repair proteins required for proper cell-cycle regulation and maintenance of genomic stability. We initially evaluated whether miR-205-5p, a microRNA (miRNA) highly expressed in head and neck squamous cell carcinoma (HNSCC), targeted BRCA1 and RAD17 expression. We found that, in vitro and in vivo, BRCA1 and RAD17 are targets of miR-205-5p in HNSCC, leading to inefficient DNA repair and increased chromosomal instability. Conversely, miR-205-5p downregulation increased BRCA1 and RAD17 messenger RNA (mRNA) levels, leading to a reduction in in vivo tumor growth. Interestingly, miR-205-5p expression was significantly anti-correlated with BRCA1 and RAD17 targets. Furthermore, we documented that miR-205-5p expression was higher in tumoral and peritumoral HNSCC tissues than non-tumoral tissues in patients exhibiting reduced local re...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research

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M2 macrophages reduce the radiosensitivity of head and neck cancer by releasing HB‑EGF. Oncol Rep. 2020 Aug;44(2):698-710 Authors: Fu E, Liu T, Yu S, Chen X, Song L, Lou H, Ma F, Zhang S, Hussain S, Guo J, Sun J, Yu P, Mao X, Wei L Abstract The aim of the present study was to examine the potential role of human heparin‑binding epidermal growth factor (HB‑EGF) secreted by M2 macrophages in the development of radioresistance in head and neck squamous cell carcinoma (HNSCC). Immunohistochemistry was used to detect radiosensitivity in human papilloma virus (HPV)‑positive and HPV‑negative HNSCC ti...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
gmann Cordes The treatment resistance of cancer cells is a multifaceted process in which DNA repair emerged as a potential therapeutic target. DNA repair is predominantly conducted by nuclear events; yet, how extra-nuclear cues impact the DNA damage response is largely unknown. Here, using a high-throughput RNAi-based screen in three-dimensionally-grown cell cultures of head and neck squamous cell carcinoma (HNSCC), we identified novel focal adhesion proteins controlling DNA repair, including the intermediate filament protein, synemin. We demonstrate that synemin critically regulates the DNA damage response by non-h...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
nscher Hartmut Schlüter Till Sebastian Clauditz Thorsten Rieckmann Squamous cell carcinoma of the head and neck (HNSCC) consist of two distinct biological entities. While the numbers of classical, tobacco-induced HNSCC are declining, tumors caused by human papillomavirus (HPV) infection are increasing in many countries. HPV-positive HNSCC mostly arise in the oropharynx and are characterized by an enhanced sensitivity towards radiotherapy and a favorable prognosis. To identify molecular differences between both entities on the protein level, we conducted a mass spectrometric comparison of eight HPV-positive a...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
rsons The response of head and neck squamous cell carcinoma (HNSCC) to radiotherapy depends on human papillomavirus type 16 (HPV) status, and where improved outcome and survival is observed in HPV-positive disease. However, strategies to further radiosensitise the tumours, particularly relatively radioresistant HPV-negative HNSCC, are actively being sought. The impact of targeting the major protein kinases involved in the signaling of DNA double-strand break (DSB) repair, namely ataxia telangiectasia-mutated (ATM), ataxia telangiectasia and Rad3-related (ATR), and the catalytic subunit of DNA-dependent protein kinase (...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
This study aimed to investigate the association between Arg399Gln SNP and the risk of squamous cell carcinoma of the head and neck. MATERIAL AND METHOD: Ninety nine patients with squamous cell carcinomas of the head and neck and 89 healthy adult controls were enrolled in this study. The Arg399Gln in XRCC1 allele was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: In the single-locus analyses, Arg399Gln SNP showed a significant association with head and neck cancer risk (p value = 0.016 and odd ratio of 1.8). On the genotype level, we applied three analysis models,...
Source: Asian Pacific Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Asian Pac J Cancer Prev Source Type: research
The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down approach, matched radiosensitive and radioresistant SQD9 cells were generated and metabolically compared, focusing on glycolysis, oxidative phosphorylation (OXPHOS) and ROS production. The cell cycle, clonogenicity, tumor growth in mice and DNA damage-repair were assessed. Mitoc...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Dikomey Wittig Arenz The PI3K/Akt/mTOR pathway is frequently altered in human papillomavirus (HPV)-positive and negative squamous cell carcinoma of the head and neck (HNSCC) and overstimulation is associated with poor prognosis. PI3K drives Akt activation and constitutive signaling acts pro-proliferative, supports cell survival, DNA repair, and contributes to radioresistance. Since the small molecule NVP-BEZ235 (BEZ235) is a potent dual inhibitor of this pathway, we were interested whether BEZ235 could be an efficient radiosensitizer. The 50 nM BEZ235 was found to abrogate endogenous and irradiation-induced pho...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Abstract Many studies have shown that TP53 mutations play a negative role in antitumor immunity. However, a few studies reported that TP53 mutations could promote antitumor immunity. To explain these contradictory findings, we analyzed five cancer cohorts from The Cancer Genome Atlas (TCGA) project. We found that TP53-mutated cancers had significantly higher levels of antitumor immune signatures than TP53-wildtype cancers in breast invasive carcinoma (BRCA) and lung adenocarcinoma (LUAD). In contrast, TP53-mutated cancers had significantly lower antitumor immune signature levels than TP53-wildtype cancers in stoma...
Source: DNA Repair - Category: Genetics & Stem Cells Authors: Tags: DNA Repair (Amst) Source Type: research
ConclusionsERCC1 expression is a well-established biomarker for cisplatin resistance. Our study demonstrates that wtHRASov tumours represent a distinctive entity that strongly express ERCC1 and can be resensitized to cisplatin by tipifarnib.Legal entity responsible for the studyThe authors.FundingKura Oncology.DisclosureT. Rampias: Research grant / Funding (institution): Kura Oncology Company. All other authors have declared no conflicts of interest.
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
In this study, two cultured head and neck squamous cell carcinoma cell lines from the same donor, UM-SCC-74A and UM-SCC-74B, were first genotyped using STR, and assessed for radiation response by the means of clonogenic survival and growth inhibition assays. Thereafter, cells were cultured, irradiated and collected for subsequent metabolic profiling analyses using liquid chromatography-mass spectrometry (LC-MS). STR verified the similarity of UM-SCC-74A and UM-SCC-74B cells, and three independent assays proved UM-SCC-74B to be clearly more radioresistant than UM-SCC-74A. The LC-MS metabolic profiling demonstrated significa...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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