Targeting Fatty Acid Amide Hydrolase Counteracts the Epithelial-to-Mesenchymal Transition in Keratinocyte-Derived Tumors
Abstract
:1. Introduction
2. Results
2.1. Inhibition of FAAH Induced by URB597 Downregulates Proliferative Capacity and Increases Anandamide Levels in Primary Keratinocytes
2.2. URB597 Contrasts the IGF-1-Induced EMT Process by Regulating Vimentin Expression, E-Cadherin Localization, and Cytokine Release–Involvement of AKT/STAT3 Signaling Pathway
2.3. URB597 Contrasts the TNF-α-Induced EMT Process by Modulating E-Cadherin Localization and by Promoting Keratinocyte Differentiation
2.4. URB597 Reduces the Proliferative and Migratory Potential and Counteracts the EMT Process in the A431 Squamous Carcinoma Cell Line
2.5. URB597 Modulates the Profile of Pro-Tumorigenic Lipid Species in A431 Cancer Cells
3. Discussion
4. Materials and Methods
4.1. Cell Cultures, Ex Vivo Skin Explants, and Treatments
4.2. Neutral Red Assay
4.3. Immunofluorescence Analysis
4.4. Immunohistochemical Analysis
4.5. Western Blot Analysis
4.6. Protein Determination Using Sandwich Enzyme-Linked Immunosorbent Assay (ELISA)
4.7. RNA Extraction and Real-Time RT-PCR
4.8. Scratch Assay
4.9. Lipid Extraction
4.10. AEA High-Performance Liquid Chromatography/Mass Spectrometry
4.11. Assessment of Pro-Inflammatory Lipid Mediators by High-Performance Liquid Chromatography/Mass Spectrometry
4.12. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Gene | Oligonucleotide Sequences (5′-3′) | Amplicon Size | Accession Number |
---|---|---|---|
E-CADHERIN | F: GAACGCATTGCCACATACAC R: ATTCGGGCTTGTTGTCATTC | 118 bp | NM_004360.5 |
FIBRONECTIN | F: CCTCGAAGAGCAAGAGGCAG R: GCTTCAGGTTTACTCTCGCA | 202 bp | NM_001365522.2 |
GAPDH | F: TGCACCACCAACTGCTTAGC R: GGCATGGACTGTGGTCATGAG | 198 bp | NM_001289746 |
K6 | F: AGTCCTGCTTCTCTTC R: CTGCTGTGGCTCCTGATG | 107 bp | NM_005554.4 |
MMP-2 | F: AGAAGGCTGTGTTCTTTGCAG R: AGGCTGGTCAGTGGCTTG | 88 bp | NM_004530.6 |
MMP-9 | F: TGACAGCGACAAGAAGTG R: CAGTGAAGCGGTACATAGG | 143 bp | NM_004994.3 |
N-CADHERIN | F: GGACTATGATTACCTGAACGACTG R: AGTTAAAGCCTAGCTTCTGAATGC | 161 bp | NM_001792.5 |
SNAI1 | F: ACTATGCCGCGCTCTTTCC R: GTCGTAGGGCTGCTGGAAG | 111 bp | NM_005985.4 |
SNAI2 | F: TGGTTGCTTCAAGGACACAT R: GCAAATGCTCTGTTGCAGTG | 77 bp | NM_003068.5 |
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Kovacs, D.; Flori, E.; Bastonini, E.; Mosca, S.; Migliano, E.; Cota, C.; Zaccarini, M.; Briganti, S.; Cardinali, G. Targeting Fatty Acid Amide Hydrolase Counteracts the Epithelial-to-Mesenchymal Transition in Keratinocyte-Derived Tumors. Int. J. Mol. Sci. 2023, 24, 17379. https://doi.org/10.3390/ijms242417379
Kovacs D, Flori E, Bastonini E, Mosca S, Migliano E, Cota C, Zaccarini M, Briganti S, Cardinali G. Targeting Fatty Acid Amide Hydrolase Counteracts the Epithelial-to-Mesenchymal Transition in Keratinocyte-Derived Tumors. International Journal of Molecular Sciences. 2023; 24(24):17379. https://doi.org/10.3390/ijms242417379
Chicago/Turabian StyleKovacs, Daniela, Enrica Flori, Emanuela Bastonini, Sarah Mosca, Emilia Migliano, Carlo Cota, Marco Zaccarini, Stefania Briganti, and Giorgia Cardinali. 2023. "Targeting Fatty Acid Amide Hydrolase Counteracts the Epithelial-to-Mesenchymal Transition in Keratinocyte-Derived Tumors" International Journal of Molecular Sciences 24, no. 24: 17379. https://doi.org/10.3390/ijms242417379