scholarly journals p21-Activated Kinases in Thyroid Cancer

Endocrinology ◽  
2020 ◽  
Vol 161 (8) ◽  
Author(s):  
Luis Bautista ◽  
Christina M Knippler ◽  
Matthew D Ringel
Keyword(s):  
Breast Cancer ◽  
Thyroid Cancer ◽  
Cell Motility ◽  
Current Knowledge ◽  
Biological Functions ◽  
Cellular Functions ◽  
Cytoskeletal Rearrangement ◽  
Group I ◽  
Wide Range ◽  
The Family

Abstract The family of p21-activated kinases (PAKs) are oncogenic proteins that regulate critical cellular functions. PAKs play central signaling roles in the integrin/CDC42/Rho, ERK/MAPK, PI3K/AKT, NF-κB, and Wnt/β-catenin pathways, functioning both as kinases and scaffolds to regulate cell motility, mitosis and proliferation, cytoskeletal rearrangement, and other cellular activities. PAKs have been implicated in both the development and progression of a wide range of cancers, including breast cancer, pancreatic melanoma, thyroid cancer, and others. Here we will discuss the current knowledge on the structure and biological functions of both group I and group II PAKs, as well as the roles that PAKs play in oncogenesis and progression, with a focus on thyroid cancer and emerging data regarding BRAF/PAK signaling.

scholarly journals Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance

2017 ◽  
Vol 24 (10) ◽  
pp. R349-R366 ◽  
Author(s):  
Catherine Zabkiewicz ◽  
Jeyna Resaul ◽  
Rachel Hargest ◽  
Wen Guo Jiang ◽  
Lin Ye
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Bone Morphogenetic Proteins ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Breast Tumour ◽  
Cellular Functions ◽  
Foetal Development ◽  
Key Factor ◽  
The Right

Bone morphogenetic proteins (BMPs) belong to the TGF-β super family, and are essential for the regulation of foetal development, tissue differentiation and homeostasis and a multitude of cellular functions. Naturally, this has led to the exploration of aberrance in this highly regulated system as a key factor in tumourigenesis. Originally identified for their role in osteogenesis and bone turnover, attention has been turned to the potential role of BMPs in tumour metastases to, and progression within, the bone niche. This is particularly pertinent to breast cancer, which commonly metastasises to bone, and in which studies have revealed aberrations of both BMP expression and signalling, which correlate clinically with breast cancer progression. Ultimately a BMP profile could provide new prognostic disease markers. As the evidence suggests a role for BMPs in regulating breast tumour cellular function, in particular interactions with tumour stroma and the bone metastatic microenvironment, there may be novel therapeutic potential in targeting BMP signalling in breast cancer. This review provides an update on the current knowledge of BMP abnormalities and their implication in the development and progression of breast cancer, particularly in the disease-specific bone metastasis.

scholarly journals Sigmar1’s Molecular, Cellular, and Biological Functions in Regulating Cellular Pathophysiology

2021 ◽  
Vol 12 ◽  
Author(s):  
Richa Aishwarya ◽  
Chowdhury S. Abdullah ◽  
Mahboob Morshed ◽  
Naznin Sultana Remex ◽  
Md. Shenuarin Bhuiyan
Keyword(s):  
Protein Quality ◽  
Current Knowledge ◽  
Neuromuscular Disorder ◽  
Recessive Mutation ◽  
Biological Functions ◽  
Causative Gene ◽  
Sigma 1 Receptor ◽  
Ion Channel Regulation ◽  
Cellular Survival ◽  
Wide Range

The Sigma 1 receptor (Sigmar1) is a ubiquitously expressed multifunctional inter-organelle signaling chaperone protein playing a diverse role in cellular survival. Recessive mutation in Sigmar1 have been identified as a causative gene for neuronal and neuromuscular disorder. Since the discovery over 40 years ago, Sigmar1 has been shown to contribute to numerous cellular functions, including ion channel regulation, protein quality control, endoplasmic reticulum-mitochondrial communication, lipid metabolism, mitochondrial function, autophagy activation, and involved in cellular survival. Alterations in Sigmar1’s subcellular localization, expression, and signaling has been implicated in the progression of a wide range of diseases, such as neurodegenerative diseases, ischemic brain injury, cardiovascular diseases, diabetic retinopathy, cancer, and drug addiction. The goal of this review is to summarize the current knowledge of Sigmar1 biology focusing the recent discoveries on Sigmar1’s molecular, cellular, pathophysiological, and biological functions.

scholarly journals Group I p21-activated kinases regulate thyroid cancer cell migration and are overexpressed and activated in thyroid cancer invasion

2010 ◽  
Vol 17 (4) ◽  
pp. 989-999 ◽  
Author(s):  
Samantha K McCarty ◽  
Motoyasu Saji ◽  
Xiaoli Zhang ◽  
David Jarjoura ◽  
Alfredo Fusco ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Motility ◽  
Cell Lines ◽  
Cancer Cell ◽  
Immunohistochemical Analysis ◽  
Cancer Invasion ◽  
Human Thyroid ◽  
Thyroid Cancer Cell ◽  
Cancer Cell Motility ◽  
Group I

p21-activated kinases (PAKs) are a family of serine/threonine kinases that regulate cytoskeletal dynamics and cell motility. PAKs are subdivided into group I (PAKs 1–3) and group II (PAKs 4–6) on the basis of structural and functional characteristics. Based on prior gene expression data that predicted enhanced PAK signaling in the invasive fronts of aggressive papillary thyroid cancers (PTCs), we hypothesized that PAKs functionally regulate thyroid cancer cell motility and are activated in PTC invasive fronts. We examined PAK isoform expression in six human thyroid cancer cell lines (BCPAP, KTC1, TPC1, FTC133, C643, and SW1746) by quantitative reverse transcription-PCR and western blot. All cell lines expressed PAKs 1–4 and PAK6 mRNA and PAKs 1–4 protein; PAK6 protein was variably expressed. Samples from normal and malignant thyroid tissues also expressed PAKs 1–4 and PAK6 mRNA; transfection with the group I (PAKs 1–3) PAK-specific p21 inhibitory domain molecular inhibitor reduced transwell filter migration by ∼50% without altering viability in all cell lines (P<0.05). BCPAP and FTC133 cells were transfected with PAK1, PAK2, or PAK3-specific small interfering RNA (siRNA); only PAK1 siRNA reduced migration significantly for both cell lines. Immunohistochemical analysis of seven invasive PTCs demonstrated an increase in PAK1 and pPAK immunoactivity in the invasive fronts versus the tumor center. In conclusion, PAK isoforms are expressed in human thyroid tissues and cell lines. PAK1 regulates thyroid cancer cell motility, and PAK1 and pPAK levels are increased in PTC invasive fronts. These data implicate PAKs as regulators of thyroid cancer invasion.

Structure and properties of the Ca2+-binding CUB domain, a widespread ligand-recognition unit involved in major biological functions

2011 ◽  
Vol 439 (2) ◽  
pp. 185-193 ◽  
Author(s):  
Christine Gaboriaud ◽  
Lynn Gregory-Pauron ◽  
Florence Teillet ◽  
Nicole M. Thielens ◽  
Isabelle Bally ◽  
...  
Keyword(s):  
Binding Site ◽  
Protein Interactions ◽  
Current Knowledge ◽  
Density Lipoprotein ◽  
Extracellular Proteins ◽  
Present Review ◽  
Biological Functions ◽  
Protein Motifs ◽  
Wide Range ◽  
Cub Domain

CUB domains are 110-residue protein motifs exhibiting a β-sandwich fold and mediating protein–protein interactions in various extracellular proteins. Recent X-ray structural and mutagenesis studies have led to the identification of a particular CUB domain subset, cbCUB (Ca2+-binding CUB domain). Unlike other CUB domains, these harbour a homologous Ca2+-binding site that underlies a conserved binding site mediating ionic interaction between two of the three conserved acidic Ca2+ ligands and a basic (lysine or arginine) residue of a protein ligand, similar to the interactions mediated by the low-density lipoprotein receptor family. cbCUB-mediated protein–ligand interactions usually involve multipoint attachment through several cbCUBs, resulting in high-affinity binding through avidity, despite the low affinity of individual interactions. The aim of the present review is to summarize our current knowledge about the structure and functions of cbCUBs, which represent the majority of the known CUB repertoire and are involved in a variety of major biological functions, including immunity and development, as well as in various cancer types. Examples discussed in the present review include a wide range of soluble and membrane-associated human proteins, as well as some archaeal and invertebrate proteins. The fact that these otherwise unrelated proteins share a common Ca2+-dependent ligand-binding ability suggests a mechanism inheri-ted from very primitive ancestors. The information provided in the present review should stimulate further investigations on the crucial interactions mediated by cbCUB-containing proteins.

scholarly journals The Fast and the Furious: Golgi Contact Sites

Contact ◽  
2021 ◽  
Vol 4 ◽  
pp. 251525642110344
Author(s):  
Yotam David ◽  
Inês G. Castro ◽  
Maya Schuldiner
Keyword(s):  
Stress Responses ◽  
Metabolic Pathways ◽  
Secretory Pathway ◽  
Current Knowledge ◽  
Close Apposition ◽  
Cellular Functions ◽  
Future Directions ◽  
Contact Sites ◽  
The Past ◽  
Wide Range

Contact sites are areas of close apposition between two membranes that coordinate nonvesicular communication between organelles. Such interactions serve a wide range of cellular functions from regulating metabolic pathways to executing stress responses and coordinating organelle inheritance. The past decade has seen a dramatic increase in information on certain contact sites, mostly those involving the endoplasmic reticulum. However, despite its central role in the secretory pathway, the Golgi apparatus and its contact sites remain largely unexplored. In this review, we discuss the current knowledge of Golgi contact sites and share our thoughts as to why Golgi contact sites are understudied. We also highlight what exciting future directions may exist in this emerging field.

FAT10: Function and Relationship with Cancer

2020 ◽  
Vol 13 (3) ◽  
pp. 182-191 ◽  
Author(s):  
Senfeng Xiang ◽  
Xuejing Shao ◽  
Ji Cao ◽  
Bo Yang ◽  
Qiaojun He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hepatocellular Carcinoma ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Functional Change ◽  
Cancer Development ◽  
Cancer Cell Proliferation ◽  
Biological Functions ◽  
Carcinoma Breast ◽  
Cancer Types

Posttranslational protein modifications are known to be extensively involved in cancer, and a growing number of studies have revealed that the ubiquitin-like modifier FAT10 is directly involved in cancer development. FAT10 was found to be highly upregulated in various cancer types, such as glioma, hepatocellular carcinoma, breast cancer and gastrointestinal cancer. Protein FAT10ylation and interactions with FAT10 lead to the functional change of proteins, including proteasomal degradation, subcellular delocalization and stabilization, eventually having significant effects on cancer cell proliferation, invasion, metastasis and even tumorigenesis. In this review, we summarized the current knowledge on FAT10 and discussed its biological functions in cancer, as well as potential therapeutic strategies based on the FAT10 pathway.

scholarly journals Enhancement of sodium/iodide symporter expression in thyroid and breast cancer

2006 ◽  
Vol 13 (3) ◽  
pp. 797-826 ◽  
Author(s):  
T Kogai ◽  
K Taki ◽  
G A Brent
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Thyroid Cancer ◽  
Sodium Iodide ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Wide Range ◽  
Nis Gene ◽  
Tsh Stimulation

The sodium/iodide symporter (NIS) mediates iodide uptake in the thyroid gland and lactating breast. NIS mRNA and protein expression are detected in most thyroid cancer specimens, although functional iodide uptake is usually reduced resulting in the characteristic finding of a ‘cold’ or non-functioning lesion on a radioiodine image. Iodide uptake after thyroid stimulating hormone (TSH) stimulation, however, is sufficient in most differentiated thyroid cancer to utilize β-emitting radioactive iodide for the treatment of residual and metastatic disease. Elevated serum TSH, achieved by thyroid hormone withdrawal in athyreotic patients or after recombinant human thyrotropin administration, directly stimulates NIS gene expression and/or NIS trafficking to the plasma membrane, increasing radioiodide uptake. Approximately 10–20% differentiated thyroid cancers, however, do not express the NIS gene despite TSH stimulation. These tumors are generally associated with a poor prognosis. Reduced NIS gene expression in thyroid cancer is likely due in part, to impaired trans-activation at the proximal promoter and/or the upstream enhancer. Basal NIS gene expression is detected in about 80% breast cancer specimens, but the fraction with functional iodide transport is relatively low. Lactogenic hormones and various nuclear hormone receptor ligands increase iodide uptake in breast cancer cells in vitro, but TSH has no effect. A wide range of ‘differentiation’ agents have been utilized to stimulate NIS expression in thyroid and breast cancer using in vitro and in vivo models, and a few have been used in clinical studies. Retinoic acid has been used to stimulate NIS expression in both thyroid and breast cancer. There are similarities and differences in NIS gene regulation and expression in thyroid and breast cancer. The various agents used to enhance NIS expression in thyroid and breast cancer will be reviewed with a focus on the mechanism of action. Agents that promote tumor differentiation, or directly stimulate NIS gene expression, may result in iodine concentration in ‘scan-negative’ thyroid cancer and some breast cancer.

Quantitative and Qualitative Methods of Studying the Processes of Socialization of a Modern Teenager

2020 ◽  
pp. 102-109
Author(s):  
Svetlana Alekseevna Raschetina ◽  
Keyword(s):  
Research Methods ◽  
Interpersonal Relations ◽  
Internet Communication ◽  
Socialization Process ◽  
Wide Range ◽  
The Family ◽  
Modern Family ◽  
Making Friends ◽  
Main Support

Relevance and problem statement. Modern unstable society is characterized by narrowing the boundaries of controlled socialization and expanding the boundaries of spontaneous socialization of a teenager based on his immersion in the question arises about the importance of the family in the process of socialization of a teenager in the conditions of expanding the space of socialization. There is a need to study the role of the family in this process, to search, develop and test research methods that allow us to reveal the phenomenon of socialization from the side of its value characteristics. The purpose and methodology of the study: to identify the possibilities of a systematic and anthropological methodology for studying the role of the family in the process of socialization of adolescents in modern conditions, testing research methods: photo research on the topic “Ego – I” (author of the German sociologist H. Abels), profile update reflexive processes (by S. A. Raschetina). Materials and results of the study. The study showed that for all the problems that exist in the family of the perestroika era and in the modern family, it acts for a teenager as a value and the first (main) support in the processes of socialization. The positions well known in psychology about the importance of interpersonal relations in adolescence for the formation of attitudes towards oneself as the basis of socialization are confirmed. Today, the frontiers of making friends have expanded enormously on the basis of Internet communication. The types of activities of interest to a teenager (traditional and new ones related to digitalization) are the third pillar of socialization. Conclusion. The “Ego – I” method of photo research has a wide range of possibilities for quantitative and qualitative analysis of the socialization process to identify the value Pillars of this process.

THE VALUE OF LOVE IN THE SYSTEM OF FORMATION OF THE PROFESSIONAL MATURITY OF THE EDUCATOR

2020 ◽  
Vol 1 (10(79)) ◽  
pp. 12-18
Author(s):  
G. Bubyreva
Keyword(s):  
Russian Federation ◽  
The State ◽  
Educational Process ◽  
Wide Range ◽  
The Family ◽  
The Russian Federation ◽  
The Government ◽  
The Individual ◽  
The Right

The existing legislation determines the education as "an integral and focused process of teaching and upbringing, which represents a socially important value and shall be implemented so as to meet the interests of the individual, the family, the society and the state". However, even in this part, the meaning of the notion ‘socially significant benefit is not specified and allows for a wide range of interpretation [2]. Yet the more inconcrete is the answer to the question – "who and how should determine the interests of the individual, the family and even the state?" The national doctrine of education in the Russian Federation, which determined the goals of teaching and upbringing, the ways to attain them by means of the state policy regulating the field of education, the target achievements of the development of the educational system for the period up to 2025, approved by the Decree of the Government of the Russian Federation of October 4, 2000 #751, was abrogated by the Decree of the Government of the Russian Federation of March 29, 2014 #245 [7]. The new doctrine has not been developed so far. The RAE Academician A.B. Khutorsky believes that the absence of the national doctrine of education presents a threat to national security and a violation of the right of citizens to quality education. Accordingly, the teacher has to solve the problem of achieving the harmony of interests of the individual, the family, the society and the government on their own, which, however, judging by the officially published results, is the task that exceeds the abilities of the participants of the educational process.  The particular concern about the results of the patriotic upbringing served as a basis for the legislative initiative of the RF President V. V. Putin, who introduced the project of an amendment to the Law of RF "About Education of the Russian Federation" to the State Duma in 2020, regarding the quality of patriotic upbringing [3]. Patriotism, considered by the President of RF V. V. Putin as the only possible idea to unite the nation is "THE FEELING OF LOVE OF THE MOTHERLAND" and the readiness for every sacrifice and heroic deed for the sake of the interests of your Motherland. However, the practicing educators experience shortfalls in efficient methodologies of patriotic upbringing, which should let them bring up citizens, loving their Motherland more than themselves. The article is dedicated to solution to this problem based on the Value-sense paradigm of upbringing educational dynasty of the Kurbatovs [15].

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