Squamous cell carcinoma (SCC) of the head and neck originates from the mucosal lining of the upper aerodigestive tract, including the lip, tongue, nasopharynx, oropharynx, larynx and hypopharynx. In this review, we summarise what is currently known about the potential function of primary cilia in the pathogenesis of this disease. As primary cilia represent a key cellular structure for signal transduction and are related to cell proliferation, an understanding of their role in carcinogenesis is necessary for the design of new treatment approaches. Here, we introduce cilia-related signalling in head and neck squamous cell carcinoma (HNSCC) and its possible association with HNSCC tumorigenesis. From this point of view, PDGF, EGF, Wnt and Hh signalling are discussed as all these pathways were found to be dysregulated in HNSCC. Moreover, we review the clinical potential of small molecules affecting primary cilia signalling to target squamous cell carcinoma of the head and neck area.

• Klíčová slova
• Hedgehog, PDGF, Wnt, head and neck cancer, oral squamous cell carcinoma, primary cilium, signalling pathway inhibitors,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

In melanoma and other cancers, invasion, epithelial-to-mesenchymal transition, metastasis and cancer stem cell maintenance are regulated by transcription factors including the Snail family. Slug (Snail2) protein generally supports migration and apoptosis resistance. However, its role in melanoma is not completely understood. The present study investigated the transcriptional regulation of the SLUG gene in melanoma. It demonstrated that SLUG is under the control of the Hedgehog/GLI signaling pathway and is activated predominantly by the transcription factor GLI2. The SLUG gene promoter contains a high number of GLI-binding sites. Slug expression is activated by GLI factors in reporter assays and inhibited by GANT61 (GLI inhibitor) and cyclopamine (SMO inhibitor). SLUG mRNA levels are lowered by GANT61 as assessed by reverse transcription-quantitative PCR. Chromatin immunoprecipitation revealed abundant binding of factors GLI1-3 in the four subregions of the proximal SLUG promoter. Notably, melanoma-associated transcription factor (MITF) is an imperfect activator of the SLUG promoter in reporter assays, and downregulation of MITF had no effect on endogenous Slug protein levels. Immunohistochemical analysis confirmed the above findings and showed MITF-negative regions in metastatic melanoma that were positive for GLI2 and Slug. Taken together, the results demonstrated a previously unrecognized transcriptional activation mechanism of the SLUG gene, which may represent its main regulation of expression in melanoma cells.

• Klíčová slova
• GLI family zinc finger, Hedgehog signaling, Slug, melanoma, melanoma-associated transcription factor,
• MeSH
• apoptóza MeSH
• lidé MeSH
• melanom * genetika   MeSH
• proteiny hedgehog * genetika   MeSH
• signální transdukce MeSH
• transkripční faktory genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• proteiny hedgehog * MeSH
• transkripční faktory MeSH

Epithelial-mesenchymal transition (EMT) is a cellular mechanism used by cancer cells to acquire migratory and stemness properties. In this study, we show, through in vitro, in vivo, and 3D culture experiments, that the mitochondrial protein LACTB manifests tumor suppressor properties in ovarian cancer. We show that LACTB is significantly down-regulated in epithelial ovarian cancer cells and clinical tissues. Re-expression of LACTB negatively effects the growth of cancer cells but not of non-tumorigenic cells. Mechanistically, we show that LACTB leads to differentiation of ovarian cancer cells and loss of their stemness properties, which is achieved through the inhibition of the EMT program and the LACTB-dependent down-regulation of Snail2/Slug transcription factor. This study uncovers a novel role of LACTB in ovarian cancer and proposes new ways of counteracting the oncogenic EMT program in this model system.

• MeSH
• beta-laktamasy * genetika   metabolismus   MeSH
• epitelo-mezenchymální tranzice * genetika   MeSH
• karcinogeneze MeSH
• lidé MeSH
• membránové proteiny genetika   metabolismus   MeSH
• mitochondriální proteiny genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory vaječníků * genetika   metabolismus   patologie   MeSH
• rodina transkripčních faktorů Snail * genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• beta-laktamasy * MeSH
• LACTB protein, human MeSH Prohlížeč
• membránové proteiny MeSH
• mitochondriální proteiny MeSH
• rodina transkripčních faktorů Snail * MeSH
• SNAI2 protein, human MeSH Prohlížeč

Prostate cancer (PCa) is the second leading cause of cancer-related deaths in men in Western countries, and there is still an urgent need for a better understanding of PCa progression to inspire new treatment strategies. Skp2 is a substrate-recruiting component of the E3 ubiquitin ligase complex, whose activity is regulated through neddylation. Slug is a transcriptional repressor involved in the epithelial-to-mesenchymal transition, which may contribute to therapy resistance. Although Skp2 has previously been associated with a mesenchymal phenotype and prostate cancer progression, the relationship with Slug deserves further elucidation. We have previously shown that a high Gleason score (≥8) is associated with higher Skp2 and lower E-cadherin expression. In this study, significantly increased expression of Skp2, AR, and Slug, along with E-cadherin downregulation, was observed in primary prostate cancer in patients who already had lymph node metastases. Skp2 was slightly correlated with Slug and AR in the whole cohort (Rs 0.32 and 0.37, respectively), which was enhanced for both proteins in patients with high Gleason scores (Rs 0.56 and 0.53, respectively) and, in the case of Slug, also in patients with metastasis to lymph nodes (Rs 0.56). Coexpression of Skp2 and Slug was confirmed in prostate cancer tissues by multiplex immunohistochemistry and confocal microscopy. The same relationship between these two proteins was observed in three sets of prostate epithelial cell lines (PC3, DU145, and E2) and their mesenchymal counterparts. Chemical inhibition of Skp2, but not RNA interference, modestly decreased Slug protein in PC3 and its docetaxel-resistant subline PC3 DR12. Importantly, chemical inhibition of Skp2 by MLN4924 upregulated p27 and decreased Slug expression in PC3, PC3 DR12, and LAPC4 cells. Novel treatment strategies targeting Skp2 and Slug by the neddylation blockade may be promising in advanced prostate cancer, as recently documented for other aggressive solid tumors.

• Klíčová slova
• Skp2 (S-phase kinase-associated protein 2), Slug, immunohistochemistry, multiplex, neddylation, prostate cancer,
• MeSH
• androgenní receptory genetika   metabolismus   MeSH
• buňky PC-3 MeSH
• CD antigeny genetika   metabolismus   MeSH
• cyklopentany farmakologie   MeSH
• docetaxel farmakologie   MeSH
• epitelo-mezenchymální tranzice genetika   MeSH
• inhibitor p27 cyklin-dependentní kinasy genetika   metabolismus   MeSH
• kadheriny genetika   metabolismus   MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• nádorové buněčné linie MeSH
• nádory prostaty genetika   metabolismus   patologie   MeSH
• posttranslační úpravy proteinů * MeSH
• prostata metabolismus   patologie   MeSH
• protein NEDD8 genetika   metabolismus   MeSH
• proteiny asociované s kinázou S-fáze antagonisté a inhibitory   genetika   metabolismus   MeSH
• protinádorové látky farmakologie   MeSH
• pyrimidiny farmakologie   MeSH
• regulace genové exprese u nádorů MeSH
• rodina transkripčních faktorů Snail genetika   metabolismus   MeSH
• stupeň nádoru MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androgenní receptory MeSH
• CD antigeny MeSH
• CDH1 protein, human MeSH Prohlížeč
• cyklopentany MeSH
• docetaxel MeSH
• inhibitor p27 cyklin-dependentní kinasy MeSH
• kadheriny MeSH
• malá interferující RNA MeSH
• NEDD8 protein, human MeSH Prohlížeč
• pevonedistat MeSH Prohlížeč
• protein NEDD8 MeSH
• proteiny asociované s kinázou S-fáze MeSH
• protinádorové látky MeSH
• pyrimidiny MeSH
• rodina transkripčních faktorů Snail MeSH
• SKP2 protein, human MeSH Prohlížeč
• SNAI1 protein, human MeSH Prohlížeč

Excessive connective tissue accumulation, a hallmark of hypertrophic scaring, results in progressive deterioration of the structure and function of organs. It can also be seen during tumor growth and other fibroproliferative disorders. These processes result from a wide spectrum of cross-talks between mesenchymal, epithelial and inflammatory/immune cells that have not yet been fully understood. In the present review, we aimed to describe the molecular features of fibroblasts and their interactions with immune and epithelial cells and extracellular matrix. We also compared different types of fibroblasts and their roles in skin repair and regeneration following burn injury. In summary, here we briefly review molecular changes underlying hypertrophic scarring following burns throughout all basic wound healing stages, i.e. during inflammation, proliferation and maturation.

• Klíčová slova
• burn, cell interaction, pathological scar, skin, stem cell, wound healing,
• MeSH
• epitelové buňky metabolismus   patologie   MeSH
• extracelulární matrix metabolismus   patologie   MeSH
• fibroblasty metabolismus   patologie   MeSH
• hojení ran genetika   MeSH
• jizva hypertrofická genetika   imunologie   patologie   MeSH
• lidé MeSH
• popálení genetika   patologie   MeSH
• proliferace buněk genetika   MeSH
• zánět genetika   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH