scholarly journals The Context-Dependent Impact of Integrin-Associated CD151 and Other Tetraspanins on Cancer Development and Progression: A Class of Versatile Mediators of Cellular Function and Signaling, Tumorigenesis and Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2005
Author(s):  
Sonia Erfani ◽  
Hui Hua ◽  
Yueyin Pan ◽  
Binhua P. Zhou ◽  
Xiuwei H. Yang
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Wide Spectrum ◽  
Tumor Development ◽  
Cell Lineage ◽  
Integral Membrane Proteins ◽  
Multiple Cancer ◽  
Mesenchymal Transition ◽  
Current Review ◽  
Cancer Types

As a family of integral membrane proteins, tetraspanins have been functionally linked to a wide spectrum of human cancers, ranging from breast, colon, lung, ovarian, prostate, and skin carcinomas to glioblastoma. CD151 is one such prominent member of the tetraspanin family recently suggested to mediate tumor development, growth, and progression in oncogenic context- and cell lineage-dependent manners. In the current review, we summarize recent advances in mechanistic understanding of the function and signaling of integrin-associated CD151 and other tetraspanins in multiple cancer types. We also highlight emerging genetic and epigenetic evidence on the intrinsic links between tetraspanins, the epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs), and the Wnt/β-catenin pathway, as well as the dynamics of exosome and cellular metabolism. Finally, we discuss the implications of the highly plastic nature and epigenetic susceptibility of CD151 expression, function, and signaling for clinical diagnosis and therapeutic intervention for human cancer.

scholarly journals Integrated Genomic Analysis of Hypoxia Genes across Cancer Types Identifies Significant Associations with Cancer Hallmarks

2018 ◽  
Author(s):  
Lingjian Yang ◽  
Laura Forker ◽  
Christina S. Fjeldbo ◽  
Robert G. Bristow ◽  
Heidi Lyng ◽  
...  
Keyword(s):  
Environmental Factor ◽  
Epithelial Mesenchymal Transition ◽  
Tumour Progression ◽  
The Cancer Genome Atlas ◽  
Silent Mutation ◽  
Multiple Cancer ◽  
Mesenchymal Transition ◽  
Cancer Types ◽  
Pan Cancer

ABSTRACTHypoxia is a generic micro-environmental factor in most solid tumours. While most published literature focused on in vitro or single tumour type investigations, we carried out the first multi-omics pan cancer analysis of hypoxia with the aim of gaining a comprehensive understanding of its implication in tumour biology. A core set of 52 mRNAs were curated based on experimentally validated hypoxia gene sets from multiple cancer types. The 52 mRNAs collectively stratified high- and low-hypoxia tumours from The Cancer Genome Atlas (TCGA) database (9698 primary tumours) in each of the 32 cancer types available. High- hypoxia tumours had high expression of not only mRNA but also protein and microRNA markers of hypoxia. In a pan cancer transcriptomic analysis, ≥70% of the known cancer hallmark pathways were enriched in high-hypoxia tumours, most notably epithelial mesenchymal transition potential, proliferation (G2M checkpoint, E2F targets, MYC targets) and immunology response. In a multi-omics analysis, gene expression-determined high- hypoxia tumours had a higher non-silent mutation rate, DNA damage repair deficiency and leukocyte infiltration. The associations largely remained significant after correcting for confounding factors, showing a profound impact of hypoxia in tumour evolution across cancer types. High-hypoxia tumours determined using the core gene set had a poor prognosis in 16/32 cancer types, with statistical significances remaining in five after adjusting for tumour stage and omics biomarkers. In summary, this first comprehensive in vivo map of hypoxia in cancers highlights the importance of this micro-environmental factor in driving tumour progression.

scholarly journals Tumor Suppressive Effects of miR-124 and Its Function in Neuronal Development

2021 ◽  
Vol 22 (11) ◽  
pp. 5919
Author(s):  
Rikako Sanuki ◽  
Tomonori Yamamura
Keyword(s):  
Target Genes ◽  
Neuronal Development ◽  
Epithelial Mesenchymal Transition ◽  
Cell Lineage ◽  
Suppressive Effect ◽  
Breast Cancers ◽  
Mesenchymal Transition ◽  
Cell Metastasis ◽  
Wide Range ◽  
Cancer Types

MicroRNA-124 (miR-124) is strongly expressed in neurons, and its expression increases as neurons mature. Through DNA methylation in the miR-124 promoter region and adsorption of miR-124 by non-coding RNAs, miR-124 expression is known to be reduced in many cancer cells, especially with high malignancy. Recently, numerous studies have focused on miR-124 due to its promising tumor-suppressive effects; however, the overview of their results is unclear. We surveyed the tumor-suppressive effect of miR-124 in glial cell lineage cancers, which are the most frequently reported cancer types involving miR-124, and in lung, colon, liver, stomach, and breast cancers, which are the top five causes of cancer death. Reportedly, miR-124 not only inhibits proliferation and accelerates apoptosis, but also comprehensively suppresses tumor malignant transformation. Moreover, we found that miR-124 exerts its anti-tumor effects by regulating a wide range of target genes, most notably STAT3 and EZH2. In addition, when compared to the original role of miR-124 in neuronal development, we found that the miR-124 target genes that contribute to neuronal maturation share similarities with genes that cause cancer cell metastasis and epithelial-mesenchymal transition. We believe that the two apparently unrelated fields, cancer and neuronal development, can bring new discoveries to each other through the study of miR-124.

scholarly journals Pan-Cancer Analysis of VIM Expression in Human Cancer Tissues

2021 ◽  
Author(s):  
Małgorzata Blatkiewicz ◽  
Piotr Białas ◽  
Olga Taryma-Leśniak ◽  
Beata Hukowska-Szematowicz
Keyword(s):  
Protein Interactions ◽  
Promoter Methylation ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Gene Promoter ◽  
The Cancer Genome Atlas ◽  
Intermediate Filament Protein ◽  
Biological Regulation ◽  
Mesenchymal Transition ◽  
Cancer Types

Abstract In 2020, more than 19 million cancer cases were diagnosed. One of the best paths to more effective treatment with a chance of being cured for patients is early detection. Vimentin (VIM), as an intermediate filament protein, is broadly expressed in mesenchymal cells. VIM is responsible for several biological processes such as cellular component organization and biogenesis, metabolic processes, and biological regulation. A growing body of literature indicates that expression of the VIM gene (VIM) is disrupted in carcinomas during epithelial–mesenchymal transition. Herein, we broadly analyzed the gene expression and promoter methylation profile of VIM in 19 cancer types across The Cancer Genome Atlas (TCGA). Furthermore, the protein–protein interactions (GeneMANIA and Search Tool for the Retrieval of Interacting Genes (STRING) database) and the alteration frequency of mutations (cBioPortal database) in VIM were analyzed. We proved that VIM is overexpressed in seven of the 19 studied cancer types. For two of them, we observed an association of VIM expression with gene promoter methylation. It must be emphasized that VIM overexpression can be a potential diagnostic biomarker in selected types of cancers.

scholarly journals CancerImmunityQTL: a database to systematically evaluate the impact of genetic variants on immune infiltration in human cancer

2020 ◽  
Vol 49 (D1) ◽  
pp. D1065-D1073
Author(s):  
Jianbo Tian ◽  
Yimin Cai ◽  
Yue Li ◽  
Zequn Lu ◽  
Jinyu Huang ◽  
...  
Keyword(s):  
Immune Cells ◽  
Genetic Variants ◽  
Immune Cell ◽  
Human Cancer ◽  
Tumor Development ◽  
Multiple Cancer ◽  
Immune Infiltration ◽  
Cancer Types ◽  
Cell Fractions ◽  
The Impact

Abstract Tumor-infiltrating immune cells as integral component of the tumor microenvironment are associated with tumor progress, prognosis and responses to immunotherapy. Genetic variants have been demonstrated to impact tumor-infiltrating, underscoring the heritable character of immune landscape. Therefore, identification of immunity quantitative trait loci (immunQTLs), which evaluate the effect of genetic variants on immune cells infiltration, might present a critical step toward fully understanding the contribution of genetic variants in tumor development. Although emerging studies have demonstrated the determinants of germline variants on immune infiltration, no database has yet been developed to systematically analyze immunQTLs across multiple cancer types. Using genotype data from TCGA database and immune cell fractions estimated by CIBERSORT, we developed a computational pipeline to identify immunQTLs in 33 cancer types. A total of 913 immunQTLs across different cancer types were identified. Among them, 5 immunQTLs are associated with patient overall survival. Furthermore, by integrating immunQTLs with GWAS data, we identified 527 immunQTLs overlapping with known GWAS linkage disequilibrium regions. Finally, we constructed a user-friendly database, CancerImmunityQTL (http://www.cancerimmunityqtl-hust.com/) for users to browse, search and download data of interest. This database provides an informative resource to understand the germline determinants of immune infiltration in human cancer and benefit from personalized cancer immunotherapy.

Prostate Carcinogenesis: Insights in relation to Epigenetics and Inflammation.

2020 ◽  
Vol 20 ◽  
Author(s):  
Mirazkar D. Pandareesh ◽  
Vivek Hamse Kameshwar ◽  
Kullaiah K. Byrappa
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Control Cell ◽  
Diagnosis And Treatment ◽  
Epigenetic Changes ◽  
Mesenchymal Transition ◽  
Prostate Carcinogenesis ◽  
History Of ◽  
Clinical Potential

: Prostate cancer is a multifactorial disease that mainly occurs due to the accumulation of somatic, genetic and epigenetic changes, resulting in the inactivation of tumor-suppressor genes and activation of oncogenes. Mutations in genes, specifically those that control cell growth and division or the repair of damaged DNA, make the cells grow and divide uncontrollably to form a tumor. The risk of developing prostate cancer depends upon the gene that has undergone the mutation. Identifying such genetic risk factors for prostate cancer pose a challenge for the researchers. Besides genetic mutations, many epigenetic alterations including DNA methylation, histone modifications (methylation, acetylation, ubiquitylation, sumoylation, and phosphorylation) nucleosomal remodelling, and chromosomal looping, have been significantly contributed to the onset of prostate cancer as well as the prognosis, diagnosis, and treatment of prostate cancer. Chronic inflammation also plays a major role in the onset and progression of human cancer, via. modifications in the tumor microenvironment by initiating epithelial-mesenchymal transition and remodelling the extracellular matrix. In this article, the authors present a brief history of the mechanisms and potential links between the genetic aberrations, epigenetic changes, inflammation and inflammasomes that are known to contribute to the prognosis of prostate cancer. Furthermore, the authors examine and discuss clinical potential of prostate carcinogenesis in relation to epigenetics and inflammation for its diagnosis and treatment.

scholarly journals Crk and CrkL as Therapeutic Targets for Cancer Treatment

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 739
Author(s):  
Taeju Park
Keyword(s):  
Tumor Cell ◽  
Cancer Treatment ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Therapeutic Targets ◽  
Viral Oncoprotein ◽  
Mesenchymal Transition ◽  
Chemotherapy Drugs ◽  
Cell Functions

Crk and CrkL are cellular counterparts of the viral oncoprotein v-Crk. Crk and CrkL are overexpressed in many types of human cancer, correlating with poor prognosis. Furthermore, gene knockdown and knockout of Crk and CrkL in tumor cell lines suppress tumor cell functions, including cell proliferation, transformation, migration, invasion, epithelial-mesenchymal transition, resistance to chemotherapy drugs, and in vivo tumor growth and metastasis. Conversely, overexpression of tumor cells with Crk or CrkL enhances tumor cell functions. Therefore, Crk and CrkL have been proposed as therapeutic targets for cancer treatment. However, it is unclear whether Crk and CrkL make distinct or overlapping contributions to tumor cell functions in various cancer types because Crk or CrkL have been examined independently in most studies. Two recent studies using colorectal cancer and glioblastoma cells clearly demonstrated that Crk and CrkL need to be ablated individually and combined to understand distinct and overlapping roles of the two proteins in cancer. A comprehensive understanding of individual and overlapping roles of Crk and CrkL in tumor cell functions is necessary to develop effective therapeutic strategies. This review systematically discusses crucial functions of Crk and CrkL in tumor cell functions and provides new perspectives on targeting Crk and CrkL in cancer therapy.

scholarly journals Effect of PACAP on Hypoxia-Induced Angiogenesis and Epithelial–Mesenchymal Transition in Glioblastoma

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 965
Author(s):  
Grazia Maugeri ◽  
Agata Grazia D’Amico ◽  
Salvatore Saccone ◽  
Concetta Federico ◽  
Daniela Maria Rasà ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Matrix Metalloproteinase 2 ◽  
Mesenchymal Transition ◽  
Hypoxic Area ◽  
Vitro Model ◽  
Human Gbm ◽  
Endothelial Growth Factor

Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts different effects in various human cancer. In glioblastoma (GBM), PACAP has been shown to interfere with the hypoxic micro-environment through the modulation of hypoxia-inducible factors via PI3K/AKT and MAPK/ERK pathways inhibition. Considering that hypoxic tumor micro-environment is strictly linked to angiogenesis and Epithelial–Mesenchymal transition (EMT), in the present study, we have investigated the ability of PACAP to regulate these events. Results have demonstrated that PACAP and its related receptor, PAC1R, are expressed in hypoxic area of human GBM colocalizing either in epithelial or mesenchymal cells. By using an in vitro model of GBM cells, we have observed that PACAP interferes with hypoxic/angiogenic pathway by reducing vascular-endothelial growth factor (VEGF) release and inhibiting formation of vessel-like structures in H5V endothelial cells cultured with GBM-conditioned medium. Moreover, PACAP treatment decreased the expression of mesenchymal markers such as vimentin, matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9) as well as CD44 in GBM cells by affecting their invasiveness. In conclusion, our study provides new insights regarding the multimodal role of PACAP in GBM malignancy.

scholarly journals Long non-coding RNA FOXD2-AS1 promotes cell proliferation, metastasis and EMT in glioma by sponging miR-506-5p

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 921-931
Author(s):  
Juan Zhao ◽  
Xue-Bin Zeng ◽  
Hong-Yan Zhang ◽  
Jie-Wei Xiang ◽  
Yu-Song Liu
Keyword(s):  
Cell Proliferation ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Glioma Cells ◽  
Suppressor Gene ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Non Coding Rna ◽  
Long Non Coding Rna

AbstractLong non-coding RNA forkhead box D2 adjacent opposite strand RNA 1 (FOXD2-AS1) has emerged as a potential oncogene in several tumors. However, its biological function and potential regulatory mechanism in glioma have not been fully investigated to date. In the present study, RT-qPCR was conducted to detect the levels of FOXD2-AS1 and microRNA (miR)-506-5p, and western blot assays were performed to measure the expression of CDK2, cyclinE1, P21, matrix metalloproteinase (MMP)7, MMP9, N-cadherin, E-cadherin and vimentin in glioma cells. A luciferase reporter assay was performed to verify the direct targeting of miR-506-5p by FOXD2-AS1. Subsequently, cell viability was analyzed using the CCK-8 assay. Cell migration and invasion were analyzed using Transwell and wound healing assays, respectively. The results demonstrated that FOXD2-AS1 was significantly overexpressed in glioma cells, particularly in U251 cells. Knockdown of FOXD2-AS1 in glioma cells significantly inhibited cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT) and regulated the expression of CDK2, cyclinE1, P21, MMP7 and MMP9. Next, a possible mechanism for these results was explored, and it was observed that FOXD2-AS1 binds to and negatively regulates miR-506-5p, which is known to be a tumor-suppressor gene in certain human cancer types. Furthermore, overexpression of miR-506-5p significantly inhibited cell proliferation, migration, invasion and EMT, and these effects could be reversed by transfecting FOXD2-AS1 into the cells. In conclusion, our data suggested that FOXD2-AS1 contributed to glioma proliferation, metastasis and EMT via competitively binding to miR-506-5p. FOXD2-AS1 may be a promising target for therapy in patients with glioma.

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