RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/ GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS G12D -expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.mouse models | non-small-cell lung cancer | protein farnesyltransferase | protein geranylgeranyltransferase type I

The aim of this study was to explore the signatures of oral microbiome associated with OSCC using a random forest (RF) model. Patients and Methods: A total of 24 patients with OSCC were enrolled in the study. The oral microbiome was assessed in cancerous lesions and matched paracancerous tissues from each patient using 16S rRNA gene sequencing. Signatures of mucosal microbiome in OSCC were identified using a RF model. Results: Significant differences were found between OSCC lesions and matched paracancerous tissues with respect to the microbial profile and composition. Linear discriminant analysis effect size analyses (LEfSe) identified 15 bacteria genera associated with cancerous lesions. Fusobacterium, Treponema, Streptococcus, Peptostreptococcus, Carnobacterium, Tannerella, Parvimonas and Filifactor were enriched. A classifier based on RF model identified a microbial signature comprising 12 bacteria, which was capable of distinguishing cancerous lesions and paracancerous tissues (AUC = 0.82). The network of the oral microbiome in cancerous lesions appeared to be simplified and fragmented. Functional analyses of oral microbiome showed altered functions in amino acid metabolism and increased capacity of glucose utilization in OSCC. Conclusion: The identified microbial signatures may potentially be used as a biomarker for predicting OSCC or for clinical assessment of oral cancer risk.

Aim: Galectin-3 (Gal-3) is a member of the carbohydrate-binding protein family that contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis. The aim of this study is to investigate the role of Gal-3 in human tongue cancer progression. Methods: Human tongue cancer cell lines (SCC-4 and CAL27) were transfected with a small-interfering RNA against Gal-3 (Gal-3-siRNA). The migration and invasion of the cells were examined using a scratch assay and BD BioCoat Matrigel Invasion Chamber, respectively. The mRNA and protein levels of β-catenin, Akt/pAkt, GSK-3β/pGSK-3β, MMP-9 in the cells were measured using RT-PCR and Western blotting, respectively. Results: Transient silencing of Gal-3 gene for 48 h significantly suppressed the migration and invasion of both SCC-4 and CAL27 cells. Silencing of Gal-3 gene significantly decreased the protein level of β-catenin, leaving the mRNA level of β-catenin unaffected. Furthermore, silencing Gal-3 gene significantly decreased the levels of phosphorylated Akt and GSK-3β, and suppressed the mRNA and protein levels of MMP-9 in the cells. Conclusion: Our data suggest that Gal-3 mediates the migration and invasion of tongue cancer cells in vitro via regulating the Wnt/ β-catenin signaling pathway and Akt phosphorylation.