IKK{beta}-Mediated Resistance to Skin Cancer Development Is Ink4a/Arf-Dependent

IKKβ (encoded by IKBKB) is a protein kinase that regulates the activity of numerous proteins important in several signaling pathways, such as the NF-B pathway. IKKβ exerts a protumorigenic role in several animal models of lung, hepatic, intestinal, and oral cancer. In addition, genomic and proteomic studies of human tumors also indicate that IKBKB gene is amplified or overexpressed in multiple tumor types. Here, the relevance of IKKβ in skin cancer was determined by performing carcinogenesis studies in animal models overexpressing IKKβ in the basal skin layer. IKKβ overexpression resulted in a striking resistance to skin cancer development and an increased expression of several tumor suppressor proteins, such as p53, p16, and p19. Mechanistically, this skin tumor–protective role of IKKβ is independent of p53, but dependent on the activity of the Ink4a/Arf locus. Interestingly, in the absence of p16 and p19, IKKβ-increased expression favors the appearance of cutaneous spindle cell–like squamous cell carcinomas, which are highly aggressive tumors. These results reveal that IKKβ activity prevents skin tumor development, and shed light on the complex nature of IKKβ effects on cancer progression, as IKKβ can both promote and prevent carcinogenesis depending on the cell type or molecular context. Implications: The ability of IKKβ to promote or prevent carcinogenesis suggests the need for further evaluation when targ...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Oncogenes and Tumor Suppressors Source Type: research

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CONCLUSIONS: LncRNA KCNQ1OT1 promotes the DDP resistance of tongue cancer by sponging miR-124-3p to regulate TRIM14 expression. PMID: 31957833 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
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Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
Conclusions: Surgery for elderly patients with LA-OCSCC is associated with a significant survival benefit, but the association is nonsignificant in the oldest elderly patients. No survival differences were observed between RT alone and CCRT in these elderly patients. Non-treatment should not be an option for these patients.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
ConclusionTERT promoter mutations are most likely a late event in tumor development, occurring in a context of critically short telomeres, mostly in patients with oral cavity SCC.TERT levels, but notTERT promoter mutational status impact clinical outcome.
Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
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Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
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Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
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Source: International Journal of Medical Sciences - Category: Biomedical Science Tags: Int J Med Sci Source Type: research
The oral microbiota plays an important role in the human microbiome and human health, and imbalances between microbes and their hosts can lead to oral and systemic diseases and chronic inflammation, which is usually caused by bacteria and contributes to cancer. There may be a relationship between oral bacteria and oral squamous cell carcinoma (OSCC); however, this relationship has not been thoroughly characterized. Therefore, in this study, we compared the microbiota compositions between tumor sites and opposite normal tissues in buccal mucosal of 50 patients with OSCC using the 16S rDNA sequencing. Richness and diversity ...
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Abstract Expression of cyclo-oxygenase-2 (COX-2) and protein phosphatase 2A (PP2A) deactivation occurs frequently in oral squamous cell carcinoma (OSCC). We initially assessed COX-2 and PP2A protein expression in OSCC specimens using immunohistochemical (IHC) staining and western blot analysis. We found strong COX-2 and phosphorylated PP2A (p-PP2A) expression in OSCC samples. No significant difference in total PP2A expression was observed between cancer and nontumor tissues. The effect of combining COX-2 inhibitor and celecoxib (CXB) with the PP2A inhibitor, calyculin-A (CLA) on the OSCC cell line, HSC3, was evalu...
Source: Biotechnic and Histochemistry - Category: Research Authors: Tags: Biotech Histochem Source Type: research
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Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research
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