scholarly journals Comprehensive Analysis of TGF β & β – Catenin Components in Various Human Cancer Tissues

2021 ◽  
Vol 9 (1) ◽  
pp. 29
Author(s):  
Jamila Sameer Daraghmeh ◽  
Bayan Mustafa Mansour ◽  
Asmaa Yousef Kmail ◽  
Iqab Ghalib Daraghmeh

Studies over the last years revealed significant insights into the β-Catenin & TGF β signal transduction pathways and that such pathways are abnormal activated in abundant cancer types. According to the straight forward effect of these pathways in various tumor types, both pathways are currently considered targets for innovative cancer therapies. This view study emphasizes 13 proteins that are implicated in these two pathways. As there has been widespread research into the proteins that involved in these pathways, we have utilized data existing in the Human Protein Atlas database in this paper to examine the expression of 53 crucial proteins that are recognized to be involved in the activation of these pathways in a distinct group of 45 cancer types. Our findings revealed notably that the proteins (SKIL, SHC, ERK1/2, RAS, PI3K (PIK3CA), SMAD8, ACVR2A/1B SNON, AKT, and SMAD3, from TGF β and (RNF43, SNAIL1 and DVl) for β catenin show high expression in most caner tissues. Our results strongly suggest that these proteins might have the ability to act as potential objects for remedies and provide perception into the molecular basis of cancer.

Oncotarget ◽  
2016 ◽  
Vol 7 (17) ◽  
pp. 23043-23055 ◽  
Author(s):  
Isabella Syring ◽  
Niklas Klümper ◽  
Anne Offermann ◽  
Martin Braun ◽  
Mario Deng ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2739 ◽  
Author(s):  
Yangxiu Wu ◽  
Rebecca C. Poulos ◽  
Roger R. Reddel

Telomere abnormalities facilitate cancer development by contributing to genomic instability and cellular immortalization. The Protection of Telomeres 1 (POT1) protein is an essential subunit of the shelterin telomere binding complex. It directly binds to single-stranded telomeric DNA, protecting chromosomal ends from an inappropriate DNA damage response, and plays a role in telomere length regulation. Alterations of POT1 have been detected in a range of cancers. Here, we review the biological functions of POT1, the prevalence of POT1 germline and somatic mutations across cancer predisposition syndromes and tumor types, and the dysregulation of POT1 expression in cancers. We propose a framework for understanding how POT1 abnormalities may contribute to oncogenesis in different cell types. Finally, we summarize the clinical implications of POT1 alterations in the germline and in cancer, and possible approaches for the development of targeted cancer therapies.


2020 ◽  
Author(s):  
Su Wu ◽  
Gerhard Wagner

SUMMARYEukaryotic translation initiation complex (eIF4F) plays roles so diverse in human cancers as to complicate development of an overarching understanding of eIF4F’s functional and regulatory impacts across tumor types. Our analysis of large public data sets yielded several useful findings. EIF4G1 frequently gains gene copies and is overexpressed to achieve characteristic stoichiometries with EIF4E and EIF4A1 in cancers. Varied expressions among EIF4F components distinguish malignant from healthy tissues, regardless of tissue or cancer types. EIF4G1 expression in particular correlates with poor prognosis. Tumors dysregulate biological “house-keeping” pathways typically regulated by cap-dependent initiation in healthy tissues, yet strengthen regulation of cancer-specific pathways in cap-independent contexts. In lung adenocarcinoma, altered interactions among eIF4F subunits are mechanistically linked to eIF4G1 phosphorylation. Tumors may select between cap-dependent and -independent mechanisms, through eIF4G1’s adaptable interactions with eIF4F subunits. Collectively, these results are an important advance towards a general model of translation initiation in cancer.


Science ◽  
2020 ◽  
Vol 368 (6494) ◽  
pp. 973-980 ◽  
Author(s):  
Deborah Nejman ◽  
Ilana Livyatan ◽  
Garold Fuks ◽  
Nancy Gavert ◽  
Yaara Zwang ◽  
...  

Bacteria were first detected in human tumors more than 100 years ago, but the characterization of the tumor microbiome has remained challenging because of its low biomass. We undertook a comprehensive analysis of the tumor microbiome, studying 1526 tumors and their adjacent normal tissues across seven cancer types, including breast, lung, ovary, pancreas, melanoma, bone, and brain tumors. We found that each tumor type has a distinct microbiome composition and that breast cancer has a particularly rich and diverse microbiome. The intratumor bacteria are mostly intracellular and are present in both cancer and immune cells. We also noted correlations between intratumor bacteria or their predicted functions with tumor types and subtypes, patients’ smoking status, and the response to immunotherapy.


2018 ◽  
Author(s):  
Yuwei Zhang ◽  
Yang Tao ◽  
Huihui Ji ◽  
Wei Li ◽  
Xingli Guo ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1343
Author(s):  
Gagan Chhabra ◽  
Chandra K. Singh ◽  
Deeba Amiri ◽  
Neha Akula ◽  
Nihal Ahmad

Immunomodulation of the tumor microenvironment is emerging as an important area of research for the treatment of cancer patients. Several synthetic and natural agents are being investigated for their ability to enhance the immunogenic responses of immune cells present in the tumor microenvironment to impede tumor cell growth and dissemination. Among them, resveratrol, a stilbenoid found in red grapes and many other natural sources, has been studied extensively. Importantly, resveratrol has been shown to possess activity against various human diseases, including cancer. Mechanistically, resveratrol has been shown to regulate an array of signaling pathways and processes involving oxidative stress, inflammation, apoptosis, and several anticancer effects. Furthermore, recent research suggests that resveratrol can regulate various cellular signaling events including immune cell regulation, cytokines/chemokines secretion, and the expression of several other immune-related genes. In this review, we have summarized recent findings on resveratrol’s effects on immune regulatory cells and associated signaling in various cancer types. Numerous immunomodulatory effects of resveratrol suggest it may be useful in combination with other cancer therapies including immunotherapy for effective cancer management.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ruijuan Du ◽  
Chuntian Huang ◽  
Kangdong Liu ◽  
Xiang Li ◽  
Zigang Dong

AbstractAurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.


Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 433
Author(s):  
Bijesh George ◽  
P. Mukundan Pillai ◽  
Aswathy Mary Paul ◽  
Revikumar Amjesh ◽  
Kim Leitzel ◽  
...  

To define the growing significance of cellular targets and/or effectors of cancer drugs, we examined the fitness dependency of cellular targets and effectors of cancer drug targets across human cancer cells from 19 cancer types. We observed that the deletion of 35 out of 47 cellular effectors and/or targets of oncology drugs did not result in the expected loss of cell fitness in appropriate cancer types for which drugs targeting or utilizing these molecules for their actions were approved. Additionally, our analysis recognized 43 cellular molecules as fitness genes in several cancer types in which these drugs were not approved, and thus, providing clues for repurposing certain approved oncology drugs in such cancer types. For example, we found a widespread upregulation and fitness dependency of several components of the mevalonate and purine biosynthesis pathways (currently targeted by bisphosphonates, statins, and pemetrexed in certain cancers) and an association between the overexpression of these molecules and reduction in the overall survival duration of patients with breast and other hard-to-treat cancers, for which such drugs are not approved. In brief, the present analysis raised cautions about off-target and undesirable effects of certain oncology drugs in a subset of cancers where the intended cellular effectors of drug might not be good fitness genes and that this study offers a potential rationale for repurposing certain approved oncology drugs for targeted therapeutics in additional cancer types.


Author(s):  
Anika Tabassum ◽  
Md. Nazmus Samdani ◽  
Tarak Chandra Dhali ◽  
Rahat Alam ◽  
Foysal Ahammad ◽  
...  

Abstract Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. Key messages • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.


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