scholarly journals Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

2021 ◽  
Author(s):  
Oscar Urtatiz ◽  
Amanda Haage ◽  
Guy Tanentzapf ◽  
Catherine D. Van Raamsdonk
Keyword(s):  
Signaling Pathway ◽  
Gene Expression Analysis ◽  
Cell Of Origin ◽  
Uveal Tract ◽  
Downstream Effector ◽  
Suppressor Mutations ◽  
Differential Gene ◽  
Melanoma Subtypes ◽  
Overlapping Sets ◽  
Common Cell

Different melanoma subtypes exhibit specific and non-overlapping sets of oncogene and tumor suppressor mutations, despite a common cell of origin in melanocytes. For example, activation of the Gαq/11 signaling pathway is a characteristic initiating event in primary melanomas that arise in the dermis, uveal tract or central nervous system. It is rare in melanomas arising in the epidermis. Here, we present evidence that in the mouse, crosstalk with the epidermal microenvironment actively impairs the survival of melanocytes expressing the GNAQQ209L oncogene, providing a new model for oncogene specificity in cancer. The presence of epidermal cells inhibited cell division and fragmented dendrites of melanocytes expressing GNAQQ209L in culture, while they promoted the growth of normal melanocytes. Differential gene expression analysis of FACS sorted epidermal melanocytes showed that cells expressing GNAQQ209L exhibit an oxidative stress and apoptosis signature previously linked to vitiligo. Furthermore, PLCB4, the direct downstream effector of Gαq/11 signaling, is frequently mutated in cutaneous melanoma alongside P53 and NF1. Our results suggest that a deficiency of PLCB4 promotes cutaneous melanomagenesis by reducing GNAQ driven signaling. Hence, our studies reveal the flip side of the GNAQ/PLCB4 signaling pathway, which was hitherto unsuspected. In the future, understanding how epidermal crosstalk restrains the GNAQQ209L oncogene could suggest novel melanoma therapies.

scholarly journals Crosstalk with keratinocytes causes GNAQ oncogene specificity in melanoma

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Oscar Urtatiz ◽  
Amanda Haage ◽  
Guy Tanentzapf ◽  
Catherine D Van Raamsdonk
Keyword(s):  
Central Nervous System ◽  
Novel Therapies ◽  
Cell Of Origin ◽  
Present Evidence ◽  
Uveal Tract ◽  
Suppressor Mutations ◽  
Interfollicular Epidermis ◽  
Melanoma Subtypes ◽  
Overlapping Sets ◽  
Common Cell

Different melanoma subtypes exhibit specific and non-overlapping sets of oncogene and tumor suppressor mutations, despite a common cell of origin in melanocytes. For example, activation of the Gαq/11 signaling pathway is a characteristic initiating event in primary melanomas that arise in the dermis, uveal tract or central nervous system. It is rare in melanomas arising in the epidermis. The mechanism for this specificity is unknown. Here, we present evidence that in the mouse, crosstalk with the epidermal microenvironment actively impairs the survival of melanocytes expressing the GNAQQ209L oncogene. We found that GNAQQ209L, in combination with signaling from the interfollicular epidermis (IFE), stimulates dendrite extension, leads to actin cytoskeleton disorganization, inhibits proliferation and promotes apoptosis in melanocytes. The effect was reversible and paracrine. In contrast, the epidermal environment increased the survival of wildtype and BrafV600E expressing melanocytes. Hence, our studies reveal the flip side of Gaq/11 signaling, which was hitherto unsuspected. In the future, the identification of the epidermal signals that restrain the GNAQQ209L oncogene could suggest novel therapies for GNAQ and GNA11 mutant melanomas.

scholarly journals Transcriptome Analysis Reveals a Promotion of Carotenoid Production by Copper Ions in Recombinant Saccharomyces cerevisiae

2021 ◽  
Vol 9 (2) ◽  
pp. 233
Author(s):  
Buli Su ◽  
Anzhang Li ◽  
Ming-Rong Deng ◽  
Honghui Zhu
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Transcriptome Analysis ◽  
Gene Expression Analysis ◽  
Target Genes ◽  
Copper Ions ◽  
Carotenoid Production ◽  
Carotenoid Accumulation ◽  
Nutritional Components ◽  
Differential Gene ◽  
First Time

We previously constructed a Saccharomyces cerevisiae carotenoid producer BL03-D-4 which produced much more carotenoid in YPM (modified YPD) media than YPD media. In this study, the impacts of nutritional components on carotenoid accumulation of BL03-D-4 were investigated. When using YPM media, the carotenoid yield was increased 10-fold compared to using the YPD media. To elucidate the hidden mechanism, a transcriptome analysis was performed and showed that 464 genes changed significantly in YPM media. Furthermore, inspired by the differential gene expression analysis which indicated that ADY2, HES1, and CUP1 showed the most remarkable changes, we found that the improvement of carotenoid accumulation in YPM media was mainly due to the copper ions, since supplementation of 0.08 mM CuSO4 in YPD media could increase carotenoid yield 9.2-fold. Reverse engineering of target genes was performed and carotenoid yield could be increased 6.4-fold in YPD media through overexpression of ACE1. The present study revealed for the first time the prominent promotion of carotenoid yield by copper ions in engineered S. cerevisiae and provided a new target ACE1 for genetic engineering of S. cerevisiae for the bioproduction of carotenoids.

Differential gene expression analysis in Enchytraeus albidus exposed to natural and chemical stressors at different exposure periods

Ecotoxicology ◽  
2011 ◽  
Vol 21 (1) ◽  
pp. 213-224 ◽  
Author(s):  
Sara C. Novais ◽  
Clara F. Howcroft ◽  
Laura Carreto ◽  
Patrícia M. Pereira ◽  
Manuel A. S. Santos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Differential Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Differential Gene Expression Analysis ◽  
Differential Gene

Identification of Hub Genes Associated with Development of Lung Adenocarcinoma by Integrated Bioinformatics Analysis

2021 ◽  
Author(s):  
Jinglei Li ◽  
Wei Hou
Keyword(s):  
Gene Expression ◽  
Survival Analysis ◽  
Network Analysis ◽  
Lung Adenocarcinoma ◽  
Normal Control ◽  
Gene Expression Analysis ◽  
Normal Control Group ◽  
Control Group ◽  
Differential Gene Expression Analysis ◽  
Differential Gene

Abstract Purpose: Lung adenocarcinoma (LUAD) has high heterogeneity and poor prognosis, posing a major challenge to human health worldwide. Therefore, it is necessary to improve our understanding of the molecular mechanism of LUAD in order to be able to better predict its prognosis and develop new therapeutic strategies for target genes.Methods: The Cancer Genome Atlas and Gene Expression Omnibus, were selected to comprehensively analyze and explore the differences between LUAD tumors and adjacent normal tissues. Critical gene information was obtained through weighted gene co-expression network analysis (WGCNA), differential gene expression analysis, and survival analysis.Results: Using WGCNA and differential gene expression analysis, 29 differentially expressed genes were screened. The functional annotation analysis showed these genes to be mainly concentrated in heart trabecula formation, regulation of inflammatory response, collagen-containing extracellular matrix, and metalloendopeptidase inhibitor activity. Also, in the protein–protein interaction network analysis, 10 central genes were identified using Cytoscape's CytoHubba plug-in. The expression of CDH5, TEK, TIMP3, EDNRB, EPAS1, MYL9, SPARCL1, KLF4, and TGFBR3 in LUAD tissue was found to be lower than that in the normal control group, while the expression of MMP1 in LUAD tissue was higher than that in the normal control group. According to survival analysis, the low expression of MYL9 and SPARCL1 was correlated with poor overall survival in patients with LUAD. Finally, through the verification of the Oncomine database, it was found that the expression levels of MYL9 and SPARCL1 were consistent with the mRNA levels in LUAD samples, and both were downregulated.Conclusion: Two survival-related genes, MYL9 and SPARCL1, were determined to be highly correlated with the development of LUAD. Both may play an essential role in the development LUAD and may be potential biomarkers for its diagnosis and treatment in the future.

Sign in / Sign up

Export Citation Format

Share Document