scholarly journals SGK1 in Human Cancer: Emerging Roles and Mechanisms

2021 ◽  
Vol 10 ◽  
Author(s):  
Yiwen Sang ◽  
Piaoping Kong ◽  
Shizhen Zhang ◽  
Lingyu Zhang ◽  
Ying Cao ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Kinase Activity ◽  
Human Cancer ◽  
Therapy Resistance ◽  
Cancer Cell Proliferation ◽  
Serine Threonine Kinase ◽  
Aberrant Expression ◽  
Threonine Kinase ◽  
Cancer Types

Serum and glucocorticoid-induced protein kinase 1 (SGK1) is a member of the “AGC” subfamily of protein kinases, which shares structural and functional similarities with the AKT family of kinases and displays serine/threonine kinase activity. Aberrant expression of SGK1 has profound cellular consequences and is closely correlated with human cancer. SGK1 is considered a canonical factor affecting the expression and signal transduction of multiple genes involved in the genesis and development of many human cancers. Abnormal expression of SGK1 has been found in tissue and may hopefully become a useful indicator of cancer progression. In addition, SGK1 acts as a prognostic factor for cancer patient survival. This review systematically summarizes and discusses the role of SGK1 as a diagnostic and prognostic biomarker of diverse cancer types; focuses on its essential roles and functions in tumorigenesis, cancer cell proliferation, apoptosis, invasion, metastasis, autophagy, metabolism, and therapy resistance and in the tumor microenvironment; and finally summarizes the current understanding of the regulatory mechanisms of SGK1 at the molecular level. Taken together, this evidence highlights the crucial role of SGK1 in tumorigenesis and cancer progression, revealing why it has emerged as a potential target for cancer therapy.

scholarly journals miR-205 in Breast Cancer: State of the Art

2020 ◽  
Vol 22 (1) ◽  
pp. 27
Author(s):  
Ilaria Plantamura ◽  
Alessandra Cataldo ◽  
Giulia Cosentino ◽  
Marilena V. Iorio
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Normal Breast ◽  
Response To Therapy ◽  
Aberrant Expression ◽  
Open Questions ◽  
Tumor Tissues ◽  
Breast Physiology ◽  
Cancer Types

Despite its controversial roles in different cancer types, miR-205 has been mainly described as an oncosuppressive microRNA (miRNA), with some contrasting results, in breast cancer. The role of miR-205 in the occurrence or progression of breast cancer has been extensively studied since the first evidence of its aberrant expression in tumor tissues versus normal counterparts. To date, it is known that the expression of miR-205 in the different subtypes of breast cancer is decreasing from the less aggressive subtype, estrogen receptor/progesterone receptor positive breast cancer, to the more aggressive, triple negative breast cancer, influencing metastasis capability, response to therapy and patient survival. In this review, we summarize the most important discoveries that have highlighted the functional role of this miRNA in breast cancer initiation and progression, in stemness maintenance, in the tumor microenvironment, its potential role as a biomarker and its relevance in normal breast physiology—the still open questions. Finally, emerging evidence reveals the role of some lncRNAs in breast cancer progression as sponges of miR-205. Here, we also reviewed the studies in this field.

scholarly journals WD 40 domain of RqkA regulates its kinase activity and role in extraordinary radioresistance in Deinococcus radiodurans

2020 ◽  
Author(s):  
Dhirendra Kumar Sharma ◽  
Subhash C. Bihani ◽  
Hari S Misra ◽  
Yogendra S. Rajpurohit
Keyword(s):  
Dna Damage ◽  
Kinase Activity ◽  
Deinococcus Radiodurans ◽  
Serine Threonine Kinase ◽  
Γ Radiation ◽  
Threonine Kinase ◽  
Wd40 Domain ◽  
First Time

SummaryRqkA, a DNA damage responsive Serine / Threonine kinase is characterized for its role in DNA repair and cell division in D. radiodurans. It has a unique combination of a kinase domain at N-terminus and a WD40 type domain at C-terminus joined through a linker. WD40 domain is comprised of eight β propeller repeats held together via “tryptophan-docking motifs” and forming a typical ‘velcro’ closure structure. RqkA mutants lacking the WD40 region (hereafter referred to as WD mutant) could not complement RqkA loss in γ radiation resistance in D. radiodurans and lacked γ radiation mediated activation of kinase activity in vivo. WD mutants failed to phosphorylate its cognate substrate (e.g. DrRecA) in surrogate E. coli cells. Further, unlike wild type enzyme, the kinase activity of its WD40 mutants was not stimulated by Pyrroloquinoline quinine (PQQ) indicating the role of the WD motifs in PQQ interaction and stimulation of its kinase activity. Together, results highlighted the importance of the WD40 domain in the regulation of RqkA kinase signaling functions in vivo and thus the role of WD40 domain in the regulation of any STPK is the first time demonstrated in bacteria.ImportanceThis study highlights the importance of the WD40 domain in activity regulation and signaling activity of bacterial serine/ threonine kinase for the first time in the bacterial response to gamma radiation and DNA damage.

scholarly journals Cholesterol-Lowering Drugs on Akt Signaling for Prevention of Tumorigenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Navneet Kumar ◽  
Chandi C. Mandal
Keyword(s):  
Cancer Cells ◽  
Signaling Pathways ◽  
Tumor Development ◽  
Therapy Resistance ◽  
Review Article ◽  
Serine Threonine Kinase ◽  
Cholesterol Lowering ◽  
Threonine Kinase ◽  
Metabolic Dysregulation

Cholesterol has been reported to be accumulated in cancer cells. The metabolic dysregulation of the cholesterol is associated with tumor development and progression. The cholesterol-lowering drugs have been found to be involved in the prevention and treatment of various cancers. Akt, a serine/threonine kinase, can modulate the role of several downstream proteins involved in cell proliferation, migration, invasion, metabolism, and apoptosis. Since its involvement in several signaling pathways, its dysregulation is commonly reported in several cancers. Thus, targeting Akt could be an effective approach for cancer prevention and therapy. Cholesterol-lowering drugs have been found to affect the expression of Akt, and its activation in the cancer cells and thus have shown anticancer activity in different type of cancers. These drugs act on various signaling pathways such as PTEN/Akt, PI3k/Akt, Akt/NF-κB, Akt/FOXO1, Akt/mTOR, etc., which will be discussed in this article. This review article will discuss the significance of cholesterol in cancer cells, cholesterol-lowering drugs, the role of Akt in cancer cells, and the effects of cholesterol-lowering drugs on Akt in the prevention of therapy resistance and metastasis.

scholarly journals The Role of Notch Signaling and Leptin-Notch Crosstalk in Pancreatic Cancer

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 68 ◽  
Author(s):  
Adriana Harbuzariu ◽  
Gabriela Oprea-Ilies ◽  
Ruben Gonzalez-Perez
Keyword(s):  
Pancreatic Cancer ◽  
Notch Signaling ◽  
Cancer Progression ◽  
Treatment Success ◽  
Notch Signaling Pathway ◽  
Cancer Development ◽  
Cancer Cell Proliferation ◽  
The Novel ◽  
Cancer Types

There is accumulating evidence that deregulated Notch signaling affects cancer development, and specifically pancreatic cancer (PC) progression. Notch canonical and non-canonical signaling has diverse impact on PC. Moreover, the actions of RBP-Jk (nuclear partner of activated Notch) independent of Notch signaling pathway seem to affect differently cancer progression. Recent data show that in PC and other cancer types the adipokine leptin can modulate Notch/RBP-Jk signaling, thereby, linking the pandemic obesity with cancer and chemoresistance. The potential pivotal role of leptin on PC, and its connection with Notch signaling and chemoresistance are still not completely understood. In this review, we will describe the most important aspects of Notch-RBP-Jk signaling in PC. Further, we will discuss on studies related to RBP-Jk-independent Notch and Notch-independent RPB-Jk signaling. We will also discuss on the novel crosstalk between leptin and Notch in PC and its implications in chemoresistance. The effects of leptin-Notch/RBP-Jk signaling on cancer cell proliferation, apoptosis, and drug resistance require more investigation. Data from these investigations could help to open unexplored ways to improve PC treatment success that has shown little progress for many years.

scholarly journals Transporter associated with antigen processing 1 (TAP1) expression and prognostic analysis in breast, lung, liver, and ovarian cancer

2021 ◽  
Author(s):  
Anika Tabassum ◽  
Md. Nazmus Samdani ◽  
Tarak Chandra Dhali ◽  
Rahat Alam ◽  
Foysal Ahammad ◽  
...  
Keyword(s):  
Expression Pattern ◽  
Cancer Progression ◽  
Antigen Processing ◽  
Human Cancer ◽  
Analytical Data ◽  
Significant Negative Correlation ◽  
Cancer Tissue ◽  
Human Cancer Cell Lines ◽  
Prognostic Analysis ◽  
Cancer Types

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.

scholarly journals Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer.

2021 ◽  
Author(s):  
Amelia U. Schirmer ◽  
Lucy M. Driver ◽  
Megan T. Zhao ◽  
Carrow I. Wells ◽  
Julie E. Pickett ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Suppressor ◽  
Serine Threonine Kinase ◽  
Threonine Kinase

scholarly journals Role of the NUDT Enzymes in Breast Cancer

2021 ◽  
Vol 22 (5) ◽  
pp. 2267
Author(s):  
Roni H. G. Wright ◽  
Miguel Beato
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Cancer Progression ◽  
Breast Cancers ◽  
Metastatic Colonization ◽  
Hormone Receptor Positive ◽  
Aggressive Cancer ◽  
Cancer Types ◽  
Metastatic Process

Despite global research efforts, breast cancer remains the leading cause of cancer death in women worldwide. The majority of these deaths are due to metastasis occurring years after the initial treatment of the primary tumor and occurs at a higher frequency in hormone receptor-positive (Estrogen and Progesterone; HR+) breast cancers. We have previously described the role of NUDT5 (Nudix-linked to moiety X-5) in HR+ breast cancer progression, specifically with regards to the growth of breast cancer stem cells (BCSCs). BCSCs are known to be the initiators of epithelial-to-mesenchyme transition (EMT), metastatic colonization, and growth. Therefore, a greater understanding of the proteins and signaling pathways involved in the metastatic process may open the door for therapeutic opportunities. In this review, we discuss the role of NUDT5 and other members of the NUDT family of enzymes in breast and other cancer types. We highlight the use of global omics data based on our recent phosphoproteomic analysis of progestin signaling pathways in breast cancer cells and how this experimental approach provides insight into novel crosstalk mechanisms for stratification and drug discovery projects aiming to treat patients with aggressive cancer.

scholarly journals Bivalent Genes Targeting of Glioma Heterogeneity and Plasticity

2021 ◽  
Vol 22 (2) ◽  
pp. 540
Author(s):  
Mariam Markouli ◽  
Dimitrios Strepkos ◽  
Kostas A. Papavassiliou ◽  
Athanasios G. Papavassiliou ◽  
Christina Piperi
Keyword(s):  
Gene Expression ◽  
Cancer Progression ◽  
Integration Site ◽  
Survival Rates ◽  
Family Members ◽  
Therapy Resistance ◽  
Cellular Functions ◽  
Cns Neoplasms ◽  
Development Regulation

Gliomas account for most primary Central Nervous System (CNS) neoplasms, characterized by high aggressiveness and low survival rates. Despite the immense research efforts, there is a small improvement in glioma survival rates, mostly attributed to their heterogeneity and complex pathophysiology. Recent data indicate the delicate interplay of genetic and epigenetic mechanisms in regulating gene expression and cell differentiation, pointing towards the pivotal role of bivalent genes. Bivalency refers to a property of chromatin to acquire more than one histone marks during the cell cycle and rapidly transition gene expression from an active to a suppressed transcriptional state. Although first identified in embryonal stem cells, bivalent genes have now been associated with tumorigenesis and cancer progression. Emerging evidence indicates the implication of bivalent gene regulation in glioma heterogeneity and plasticity, mainly involving Homeobox genes, Wingless-Type MMTV Integration Site Family Members, Hedgehog protein, and Solute Carrier Family members. These genes control a wide variety of cellular functions, including cellular differentiation during early organism development, regulation of cell growth, invasion, migration, angiogenesis, therapy resistance, and apoptosis. In this review, we discuss the implication of bivalent genes in glioma pathogenesis and their potential therapeutic targeting options.

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