The secretome of skin cancer cells activates the mTOR/MYC pathway in healthy keratinocytes and induces tumorigenic properties

Hoesl, Christine; Zanuttigh, Enrica; Fröhlich, Thomas; Philippou‐Massier, Julia; Krebs, Stefan; Blum, Helmut; Dahlhoff, Maik

doi:10.1016/j.bbamcr.2020.118717

Cited by 8 publications

(4 citation statements)

References 54 publications

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“…To test this hypothesis, human skin keratinocytes were used to evaluate the survival capacity of S. pettenkoferi SP165. HaCaT is a non-transformed human keratinocyte line that has been used to investigate epithelial infection [16], cytotoxicity [17], biofilm formation [18], and skin cancer [19]. It can also be employed in models of skin wound infection where the stratum corneum is disrupted and bacteria come into close contact with living keratinocytes [18].…”

Section: S Pettenkoferi Persists In Human Keratinocytesmentioning

confidence: 99%

Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen

Ahmad-Mansour

Plumet

Huc-Brandt

et al. 2021

IJMS

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Staphylococcus pettenkoferi is a coagulase-negative Staphylococcus identified in 2002 that has been implicated in human diseases as an opportunistic pathogenic bacterium. Its multiresistant character is becoming a major health problem, yet the pathogenicity of S. pettenkoferi is poorly characterized. In this study, the pathogenicity of a S. pettenkoferi clinical isolate from diabetic foot osteomyelitis was compared with a Staphylococcus aureus strain in various in vitro and in vivo experiments. Growth kinetics were compared against S. aureus, and bacteria survival was assessed in the RAW 264.7 murine macrophage cell line, the THP-1 human leukemia monocytic cell line, and the HaCaT human keratinocyte cell line. Ex vivo analysis was performed in whole blood survival assays and in vivo assays via the infection model of zebrafish embryos. Moreover, whole-genome analysis was performed. Our results show that S. pettenkoferi was able to survive in human blood, human keratinocytes, murine macrophages, and human macrophages. S. pettenkoferi demonstrated its virulence by causing substantial embryo mortality in the zebrafish model. Genomic analysis revealed virulence factors such as biofilm-encoding genes (e.g., icaABCD; rsbUVW) and regulator-encoding genes (e.g., agr, mgrA, sarA, saeS) well characterized in S. aureus. This study thus advances the knowledge of this under-investigated pathogen and validates the zebrafish infection model for this bacterium.

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Section: S Pettenkoferi Persists In Human Keratinocytesmentioning

confidence: 99%

Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen

Ahmad-Mansour

Plumet

Huc-Brandt

et al. 2021

IJMS

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“…It was notable that a subpopulation of primary cultures (23%) of the colon adjacent to CRACs were resistant to 5FU/OXA. This suggested that malignant cells of CRAC can induce malignancy in healthy tissue, as happens in other types of cancer ( 36 ), such as breast ( 37 ), melanoma ( 38 ) and prostate ( 39 ). The fact that CSCs and fibroblasts located in the tumor supports this, and the adjacent colon export cytokines, chemokines and miRNAs, which can cause normal cells to become malignant ( 40 ).…”

Section: Discussionmentioning

confidence: 98%

Chemosensitivity analysis and study of gene resistance on tumors and cancer stem cell isolates from patients with colorectal cancer

et al. 2021

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Colorectal cancer (CRC) is one of the main causes of mortality. Recent studies suggest that cancer stem cells (CSCs) can survive after chemotherapy and promote tumor invasiveness and aggression. According to a higher hierarchy complexity of CSC, different protocols for isolation, expansion, and characterization have been used; however, there are no available resistance biomarkers that allow predicting the clinical response of treatment 5-fluorouracil (5FU) and oxaliplatin. Therefore, the primary aim of the present study was to analyze the expression of gene resistance on tumors and CSC-derived isolates from patients CRC. In the present study, adenocarcinomas of the colon and rectum (CRAC) were classified based on an in vitro adenosine triphosphate-based chemotherapy response assay, as sensitive and resistant and the percentage of CD24 and CD44 markers are evaluated by immunohistochemistry. To isolate resistant colon-CSC, adenocarcinoma tissues resistant to 5FU and oxaliplatin were evaluated. Finally, all samples were sequenced using a custom assay with chemoresistance-associated genes to find a candidate gene on resistance colon-CSC. Results showed that 59% of the CRC tissue analyzed was resistant and had a higher percentage of CD44 and CD24 markers. An association was found in the expression of some genes between the tumor-resistant tissue and CSC. Overall, isolates of the CSC population CD44 + resistant to 5FU and oxaliplatin demonstrated different expression profiles; however, the present study was able to identify overexpression of the KRT-18 gene, in most of the isolates. In conclusion, the results of the present study showed overexpression of KRT-18 in CD44 + cells is associated with chemoresistance to 5FU and oxaliplatin in CRAC.

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“…However, there is not yet agreement on the mechanisms underlying the arsenic-induced malignant transformation. It is well known that enhanced cell proliferation due to accelerated cell cycle progression may play key roles in the progression of malignant transformation induced by arsenite [ 38 , 39 ]. Low-dose arsenite can promote the proliferation of a variety of cells [ 12 , 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

MiR-96-5p Suppresses Progression of Arsenite-Induced Human Keratinocyte Proliferation and Malignant Transformation by Targeting Denticleless E3 Ubiquitin Protein Ligase Homolog

Li,

Zhao,

Yao

et al. 2023

Toxics

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Long-term exposure to arsenic has been linked to a variety of cancers, among which skin cancer is the most prevalent form. However, the mechanism underlying arsenic carcinogenesis is unclear, and there is still limited information on the role of miRNAs in arsenic-induced skin cancer. This study aims to explore the role of miR-96-5p in the arsenite-induced proliferation and malignant transformation of human HaCaT keratinocytes. The GEO database (accession numbers GSE97303, GSE97305, and GSE97306) was used to extract mRNA and miRNA expression profiles of HaCaT cells treated with or without 0.1 μmol/L sodium arsenite for 3 and 7 weeks. In this paper, according to the CCK8 assay result, HaCaT cells exposed to 0.1 μmol/L sodium arsenite for 48 h were finalized. CCK8, MTT, EdU incorporation, and colony formation assays were used to determine the viability and proliferation of HaCaT cells and transformed HaCaT (T-HaCaT) cells. The subcellular localization and relative expression levels of DTL, as well as miR-96-5p in HaCaT cells induced by arsenite, were determined via immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was performed to identify miR-96-5p bound directly to DTL. Transfection of miR-96-5p mimics or DTL siRNA was conducted to verify the arsenite-induced viability of HaCaT cells and T-HaCaT cells. T-HaCaT cells and nude mice were used to construct arsenite-induced malignant transformation and an in vivo xenograft model to demonstrate the over-expressed effect of miR-96-5p. The results showed that DTL was the target gene of miR-96-5p. Meanwhile, we also found that 0.1 μmol/L sodium arsenite upregulated DTL by decreasing the miR-96-5p level, leading to the proliferation and malignant transformation of HaCaT cells. MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer.

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The secretome of skin cancer cells activates the mTOR/MYC pathway in healthy keratinocytes and induces tumorigenic properties

Cited by 8 publications

References 54 publications

Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen

Investigating Pathogenicity and Virulence of Staphylococcus pettenkoferi: An Emerging Pathogen

Chemosensitivity analysis and study of gene resistance on tumors and cancer stem cell isolates from patients with colorectal cancer

MiR-96-5p Suppresses Progression of Arsenite-Induced Human Keratinocyte Proliferation and Malignant Transformation by Targeting Denticleless E3 Ubiquitin Protein Ligase Homolog

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