Phosphatases and solid tumors: focus on glioblastoma initiation, progression and recurrences

2017 ◽  
Vol 474 (17) ◽  
pp. 2903-2924 ◽  
Author(s):  
Matthias Dedobbeleer ◽  
Estelle Willems ◽  
Stephen Freeman ◽  
Arnaud Lombard ◽  
Nicolas Goffart ◽  
...  

Phosphatases and cancer have been related for many years now, as these enzymes regulate key cellular functions, including cell survival, migration, differentiation and proliferation. Dysfunctions or mutations affecting these enzymes have been demonstrated to be key factors for oncogenesis. The aim of this review is to shed light on the role of four different phosphatases (PTEN, PP2A, CDC25 and DUSP1) in five different solid tumors (breast cancer, lung cancer, pancreatic cancer, prostate cancer and ovarian cancer), in order to better understand the most frequent and aggressive primary cancer of the central nervous system, glioblastoma.

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yanxia Zhan ◽  
Junxian Du ◽  
Zhihui Min ◽  
Li Ma ◽  
Wei Zhang ◽  
...  

AbstractHypoxia is a common phenomenon in solid tumors. The roles of exosomes from hypoxic breast cancer stroma are less studied. So, the study was aimed to investigate the role of exosomes from hypoxic cancer-associated fibroblasts (CAFs) cells in breast cancer. The circRNA array analysis was performed to screen differential expressed circRNAs between hypoxic and normoxic CAFs exosomes. Candidate circHIF1A (circ_0032138) was screened out and it was confirmed that circHIF1A was up-regulated in the exosomes from hypoxic CAFs and their exosomes. Through investigating cellular functions including cell proliferation and stem cell features, it was demonstrated that hypoxic CAFs exosomes transferred circHIF1A into breast cancer cells, which played an important role in cancer stem cell properties sponging miR-580-5p by regulating CD44 expression. In a summary, circHIF1A from hypoxic CAFs exosomes played an important role in stem cell properties of breast cancer. CircHIF1A may act as a target molecule of breast cancer therapy.


2007 ◽  
Vol 35 (1) ◽  
pp. 133-135 ◽  
Author(s):  
N. Prevarskaya ◽  
M. Flourakis ◽  
G. Bidaux ◽  
S. Thebault ◽  
R. Skryma

A major clinical problem with PC (prostate cancer) is the cell's ability to survive and proliferate upon androgen withdrawal. Indeed, deregulated cell differentiation and proliferation, together with the suppression of apoptosis, provides the condition for abnormal tissue growth. Here, we examine the differential role of TRP (transient receptor potential) channels in the control of Ca2+ homoeostasis and growth of PC cells.


Author(s):  
Arun Kumar ◽  
Reena V Saini ◽  
Adesh K Saini

Ascorbic acid (AA) or Vitamin C is an important antioxidant which participates in numerous cellular functions. Although in human plasma its concentration is in micromolars but it reaches millimolar concentrations in most of the human tissues. The high ascorbate cellular concentrations are generated and maintained by a specific sodium-dependent Vitamin C transporter type 2 (SVCT2, member of Slc23 family). Metabolic processes recycle Vitamin C from its oxidized forms (ascorbate) inside the cells. AA concentration is highest in the neurons of the central nervous system (CNS) of mammals, and deletion of its transporter affects mice brain and overall survival. In the CNS, intracellular ascorbate serves several functions including antioxidant protection, peptide amidation, myelin formation, synaptic potentiation, and protection against glutamate toxicity. SVCT2 maintains neuronal ascorbate content in CNS which has relevance for neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s disease. As ascorbate supplements decrease infarct size in ischemia-reperfusion injury and protect neurons from oxidative damage, it is a vital dietary antioxidant. The aim of this review is to assess the role of the SVCT2 in regulating neuronal ascorbate homeostasis in CNS and the extent to which ascorbate affects brain function as an antioxidant.


2020 ◽  
Vol 13 (3) ◽  
pp. 39
Author(s):  
Irina Velikyan

The role of nuclear medicine in the management of oncological patients has expanded during last two decades. The number of radiopharmaceuticals contributing to the realization of theranostics/radiotheranostics in the context of personalized medicine is increasing. This review is focused on the examples of targeted (radio)pharmaceuticals for the imaging and therapy of neuroendocrine neoplasms (NENs), prostate cancer, and breast cancer. These examples strongly demonstrate the tendency of nuclear medicine development towards personalized medicine.


Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 382 ◽  
Author(s):  
Pradip De ◽  
Jennifer Carlson Aske ◽  
Nandini Dey

Three GTPases, RAC, RHO, and Cdc42, play essential roles in coordinating many cellular functions during embryonic development, both in healthy cells and in disease conditions like cancers. We have presented patterns of distribution of the frequency of RAC1-alteration(s) in cancers as obtained from cBioPortal. With this background data, we have interrogated the various functions of RAC1 in tumors, including proliferation, metastasis-associated phenotypes, and drug-resistance with a special emphasis on solid tumors in adults. We have reviewed the activation and regulation of RAC1 functions on the basis of its sub-cellular localization in tumor cells. Our review focuses on the role of RAC1 in cancers and summarizes the regulatory mechanisms, inhibitory efficacy, and the anticancer potential of RAC1-PAK targeting agents.


Biomedicines ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 553
Author(s):  
Jessica Maiuolo ◽  
Micaela Gliozzi ◽  
Vincenzo Musolino ◽  
Cristina Carresi ◽  
Saverio Nucera ◽  
...  

Oligodendrocytes are myelinating cells of the central nervous system which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, insulating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption a large amount of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions, including energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced, the myelination process is impaired. When myelination has finished, oligodendrocyte will have synthesized about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the dysfunction of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review, the induced malfunction of oligodendrocytes by harmful exogenous stimuli has been outlined. In particular, the effects of alcohol consumption and heavy metal intake are discussed. Furthermore, the response of the oligodendrocyte to excessive mitochondrial oxidative stress and to the altered regulation of the functioning of the endoplasmic reticulum will be explored.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Federica Brugnoli ◽  
Silvia Grassilli ◽  
Yasamin Al-Qassab ◽  
Silvano Capitani ◽  
Valeria Bertagnolo

Initially correlated with hematopoietic precursors, the surface expression of CD133 was also found in epithelial and nonepithelial cells from adult tissues in which it has been associated with a number of biological events. CD133 is expressed in solid tumors as well, including breast cancer, in which most of the studies have been focused on its use as a surface marker for the detection of cells with stem-like properties (i.e., cancer stem cells (CSCs)). Differently with other solid tumors, very limited and in part controversial are the information about the significance of CD133 in breast cancer, the most common malignancy among women in industrialized countries. In this review, we summarize the latest findings about the implication of CD133 in breast tumors, highlighting its role in tumor cells with a triple negative phenotype in which it directly regulates the expression of proteins involved in metastasis and drug resistance. We provide updates about the prognostic role of CD133, underlining its value as an indicator of increased malignancy of both noninvasive and invasive breast tumor cells. The molecular mechanisms at the basis of the regulation of CD133 levels in breast tumors have also been reviewed, highlighting experimental strategies capable to restrain its level that could be taken into account to reduce malignancy and/or to prevent the progression of breast tumors.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. TPS2640-TPS2640 ◽  
Author(s):  
Amanda D. Kaveney ◽  
Janice M. Mehnert ◽  
Antoinette R. Tan ◽  
Joseph Aisner ◽  
Rebecca Anne Moss ◽  
...  

2016 ◽  
Vol 34 (7_suppl) ◽  
pp. 295-295
Author(s):  
Simron Singh ◽  
Lorraine Lipscombe ◽  
Hadas Fischer ◽  
Jill Tinmouth ◽  
Peter Austin ◽  
...  

295 Background: The Choosing Wisely Canada (CWC) campaign aims to start conversations about unnecessary treatments and procedures in order to improve quality of care. In particular, the CWC campaign in cancer seeks to reduce interventions that are not supported by evidence and contribute to unnecessary rising costs of cancer care. We sought to document the performance of cancer screening for a new primary cancer in patients with existing metastatic cancer (CWC statement #2). Methods: We used population-based administrative health care databases from Ontario, Canada held at the Institute for Clinical Evaluative Sciences (ICES). The cohort included all adult residents of Ontario of eligible screening age (age 50 or older) diagnosed with incident, stage 4 (metastatic) colorectal cancer (CRC), lung, breast, or prostate cancer between January 1, 2007 and December 31, 2012. We examined screening tests for CRC and breast cancer in the first 1 and 3 years after diagnosis of an unrelated cancer. Given the high mortality rate in this population, screening rates were calculated using the cumulative incidence function which takes into account the competing risk of death or the occurrence of the cancer for which the patient was being screened (prior to being screened). Results: Among the 20,992 patients with stage 4 lung, breast, or prostate cancer, CRC screening within 1 year of cancer diagnosis occurred in 2.8%, 6.1%, and 13.0%, respectively. Within 3 years of diagnosis, screening rates were 3.9%, 11.9%, and 26.9%, respectively. Among the 10,034 women with metastatic CRC or lung cancer, breast cancer screening within 1 year of cancer diagnosis occurred in 8.0% and 8.7% of women, respectively. Within 3 years of diagnosis, screening rates were13.1% and 10.2%, respectively. Screening rates were higher in patients age 50-74 than those ≥75 years. Conclusions: Our findings indicate that up to one quarter of patients with metastatic cancer receive subsequent screening tests for other cancers, which are unnecessary as these patients are unlikely to benefit. Further studies are warranted to examine resource implications, potential patient and societal harms, and the future impact of the CWC campaign on this practice.


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