scholarly journals Targeting cancer stem cells in medulloblastoma by inhibiting AMBRA1 dual function in autophagy and STAT3 signalling

2021 ◽  
Author(s):  
Francesca Nazio ◽  
Agnese Po ◽  
Luana Abballe ◽  
Claudio Ballabio ◽  
Francesca Diomedi Camassei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Genetic Alterations ◽  
Dual Function ◽  
Potential Growth ◽  
Myc Oncogene ◽  
Targeted Treatments ◽  
Group 3 ◽  
And Migration ◽  
Stat3 Signalling

AbstractMedulloblastoma (MB) is a childhood malignant brain tumour comprising four main subgroups characterized by different genetic alterations and rate of mortality. Among MB subgroups, patients with enhanced levels of the c-MYC oncogene (MBGroup3) have the poorest prognosis. Here we identify a previously unrecognized role of the pro-autophagy factor AMBRA1 in regulating MB. We demonstrate that AMBRA1 expression depends on c-MYC levels and correlates with Group 3 patient poor prognosis; also, knockdown of AMBRA1 reduces MB stem potential, growth and migration of MBGroup3 stem cells. At a molecular level, AMBRA1 mediates these effects by suppressing SOCS3, an inhibitor of STAT3 activation. Importantly, pharmacological inhibition of autophagy profoundly affects both stem and invasion potential of MBGroup3 stem cells, and a combined anti-autophagy and anti-STAT3 approach impacts the MBGroup3 outcome. Taken together, our data support the c-MYC/AMBRA1/STAT3 axis as a strong oncogenic signalling pathway with significance for both patient stratification strategies and targeted treatments of MBGroup3.

scholarly journals Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

2021 ◽  
Vol 22 (16) ◽  
pp. 8470
Author(s):  
Hui Wang ◽  
Tian Tian ◽  
Jinhua Zhang
Keyword(s):  
Colorectal Cancer ◽  
Clinical Care ◽  
Inflammatory Cells ◽  
Genetic Alterations ◽  
Tumor Associated Macrophages ◽  
Invasion And Migration ◽  
Complex Process ◽  
Incidence And Mortality ◽  
And Migration

Colorectal cancer (CRC) is a malignant tumor in the digestive system whose incidence and mortality is high-ranking among tumors worldwide. The initiation and progression of CRC is a complex process involving genetic alterations in cancer cells and multiple factors from the surrounding tumor cell microenvironment. As accumulating evidence has shown, tumor-associated macrophages (TAMs)—as abundant and active infiltrated inflammatory cells in the tumor microenvironment (TME)—play a crucial role in CRC. This review focuses on the different mechanisms of TAM in CRC, including switching of phenotypical subtypes; promoting tumor proliferation, invasion, and migration; facilitating angiogenesis; mediating immunosuppression; regulating metabolism; and interacting with the microbiota. Although controversy remains in clinical evidence regarding the role of TAMs in CRC, clarifying their significance in therapy and the prognosis of CRC may shed new light on the optimization of TAM-centered approaches in clinical care.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

scholarly journals Pentraxin-3 Modulates Osteogenic/Odontogenic Differentiation and Migration of Human Dental Pulp Stem Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5778
Author(s):  
Yeon Kim ◽  
Joo-Yeon Park ◽  
Hyun-Joo Park ◽  
Mi-Kyoung Kim ◽  
Yong-Il Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dental Pulp ◽  
Tissue Repair ◽  
Therapeutic Potential ◽  
Dental Pulp Stem Cells ◽  
Pentraxin 3 ◽  
Odontogenic Differentiation ◽  
Human Dental Pulp ◽  
And Migration

Pentraxin-3 (PTX3) is recognized as a modulator of inflammation and a mediator of tissue repair. In this study, we characterized the role of PTX3 on some biological functions of human dental pulp stem cells (HDPSCs). The expression level of PTX3 significantly increased during osteogenic/odontogenic differentiation of HDPSCs, whereas the knockdown of PTX3 decreased this differentiation. Silencing of PTX3 in HDPSCs inhibited their migration and C-X-C chemokine receptor type 4 (CXCR4) expression. Our present study indicates that PTX3 is involved in osteogenic/odontogenic differentiation and migration of HDPSCs, and may contribute to the therapeutic potential of HDPSCs for regeneration and repair.

scholarly journals A Role for NF-κB in Organ Specific Cancer and Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 655 ◽  
Author(s):  
Christian Kaltschmidt ◽  
Constanze Banz-Jansen ◽  
Tahar Benhidjeb ◽  
Morris Beshay ◽  
Christine Förster ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Cancer Stem Cells ◽  
Current Knowledge ◽  
Genetic Alterations ◽  
The Status ◽  
Organ Specific ◽  
Proliferation And Metastasis ◽  
Cancer Multiple

Cancer stem cells (CSCs) account for tumor initiation, invasiveness, metastasis, and recurrence in a broad range of human cancers. Although being a key player in cancer development and progression by stimulating proliferation and metastasis and preventing apoptosis, the role of the transcription factor NF-κB in cancer stem cells is still underestimated. In the present review, we will evaluate the role of NF-κB in CSCs of glioblastoma multiforme, ovarian cancer, multiple myeloma, lung cancer, colon cancer, prostate cancer, as well as cancer of the bone. Next to summarizing current knowledge regarding the presence and contribution of CSCs to the respective types of cancer, we will emphasize NF-κB-mediated signaling pathways directly involved in maintaining characteristics of cancer stem cells associated to tumor progression. Here, we will also focus on the status of NF-κB-activity predominantly in CSC populations and the tumor mass. Genetic alterations leading to NF-κB activity in glioblastoma, ependymoma, and multiple myeloma will be discussed.

scholarly journals Isoform-Specific Role of Akt in Oral Squamous Cell Carcinoma

Biomolecules ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 253 ◽  
Author(s):  
Roy ◽  
Monisha ◽  
Padmavathi ◽  
Lalhruaitluanga ◽  
Kumar ◽  
...  
Keyword(s):  
Oral Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
B Cell Lymphoma ◽  
Genetic Alterations ◽  
Specific Role ◽  
Migration Potential ◽  
Oral Cancer Cells ◽  
And Migration

Protein kinase B (Akt) plays a very significant role in various cancers including oral cancer. However, it has three isoforms (Akt1, Akt2, and Akt3) and they perform distinct functions and even play contrasting roles in different cancers. Therefore, it becomes essential to evaluate the isoform-specific role of Akt in oral cancer. In the present study, an attempt has been made to elucidate the isoform-specific role of Akt in oral cancer. The immunohistochemical analysis of oral cancer tissues showed an overexpression of Akt1 and 2 isoforms but not Akt3. Moreover, the dataset of “The Cancer Genome Atlas” for head and neck cancer has suggested the genetic alterations of Akt1 and 2 tend to be associated with the utmost poor clinical outcome in oral cancer. Further, treatment of oral cancer cells with tobacco and its components such as benzo(a)pyrene and nicotine caused increased mRNA levels of Akt1 and 2 isoforms and also enhanced the aggressiveness of oral cancer cells in terms of proliferation, and clonogenic and migration potential. Finally, silencing of Akt1 and 2 isoforms caused decreased cell survival and induced cell cycle arrest at the G2/M phase. Akt1/2 silencing also reduced tobacco-induced aggressiveness by decreasing the clonogenic and migration potential of oral cancer cells. Moreover, silencing of Akt1 and 2 isoforms was found to decrease the expression of proteins regulating cancer cell survival and proliferation such as cyclooxygenase-2, B-cell lymphoma 2 (Bcl-2), cyclin D1, and survivin. Thus, the important role of Akt1 and 2 isoforms have been elucidated in oral cancer with in-depth mechanistic analysis.

scholarly journals The role of Src family kinases in growth and migration of glioma stem cells

2014 ◽  
Vol 45 (1) ◽  
pp. 302-310 ◽  
Author(s):  
XIAOSI HAN ◽  
WENBIN ZHANG ◽  
XIUHUA YANG ◽  
CRYSTAL G. WHEELER ◽  
CATHERINE P. LANGFORD ◽  
...  
Keyword(s):  
Stem Cells ◽  
Src Family Kinases ◽  
Glioma Stem Cells ◽  
And Migration

scholarly journals Ethical Implications in the Use of Embryonic and Adult Neural Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Rodrigo Ramos-Zúñiga ◽  
Oscar González-Pérez ◽  
Ana Macías-Ornelas ◽  
Vivian Capilla-González ◽  
Alfredo Quiñones-Hinojosa
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Neurological Diseases ◽  
Human Condition ◽  
Ethical Implications ◽  
Technological Advances ◽  
And Migration ◽  
Risk And Benefit ◽  
Proper Balance

The advent and growth of technological advances have led to new routes of knowledge. Thereby, we currently face new challenges. We have just started to get a glimpse of the structural and functional role of neural stem cells in differentiation and migration processes, the origin of synaptic networks, and subsequent readjustments in specific circuits. A whole range of treatment possibilities originates from this knowledge that potentially can be used for different neurological diseases in humans. Although this is an encouraging scenario, it implies that the human brain is the object of such study, as well as its potential manipulation and transplantation. It is, therefore, pertinent that ethical principles should be followed in such research to have proper balance between what can be done and what should be done, according to every specific context. Hence, it is wise to consider ethical implications in every research project, along with potential clinical applications, under the principle of causing no harm, following risk and benefit rules in decision making and with respect of the human condition as a priority.

scholarly journals Regulation of the differentiation and behaviour of extra-embryonic endodermal cells by basement membranes

2001 ◽  
Vol 114 (5) ◽  
pp. 931-939 ◽  
Author(s):  
P. Murray ◽  
D. Edgar
Keyword(s):  
Stem Cells ◽  
Basement Membrane ◽  
Embryonic Stem ◽  
Basement Membranes ◽  
Embryoid Bodies ◽  
Endodermal Differentiation ◽  
And Migration ◽  
The Individual ◽  
Endodermal Cells

Both the extracellular matrix and parathyroid hormone-related peptide (PTHrP) have been implicated in the differentiation and migration of extra-embryonic endodermal cells in the pre-implantation mammalian blastocyst. In order to define the individual roles and interactions between these factors in endodermal differentiation, we have used embryoid bodies derived from Lamc1(-/-) embryonic stem cells that lack basement membranes. The results show that in the absence of basement membranes, increased numbers of both visceral and parietal endodermal cells differentiate, but they fail to form organised epithelia. Furthermore, although parietal endodermal cells only migrate away from control embryoid bodies in the presence of PTHrP, they readily migrate from Lamc1(-/-) embryoid bodies in the absence of PTHrP, and this migration is unaffected by PTHrP. Thus, the basement membrane between epiblast and extra-embryonic endoderm is required for the proper organisation of visceral and parietal endodermal cells and also restricts their differentiation to maintain the population of primitive endodermal stem cells. Moreover, this basement membrane inhibits migration of parietal endodermal cells, the role of PTHrP being to stimulate delamination of parietal endodermal cells from the basement membrane rather than promoting migration per se.

scholarly journals Role of ADAM17 in invasion and migration of CD133-expressing liver cancer stem cells after irradiation

Oncotarget ◽  
2016 ◽  
Vol 7 (17) ◽  
pp. 23482-23497 ◽  
Author(s):  
Sung Woo Hong ◽  
Wonhee Hur ◽  
Jung Eun Choi ◽  
Jung-Hee Kim ◽  
Daehee Hwang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Liver Cancer ◽  
Invasion And Migration ◽  
Liver Cancer Stem Cells ◽  
And Migration

STEM CELLS IN BREAST CANCER: THE ROLE OF GENDER STEROID RECEPTORS

2020 ◽  
Vol 1 (8(77)) ◽  
pp. 11-20
Author(s):  
K. Izrailbekova
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Estrogen Receptor Alpha ◽  
Steroid Receptors ◽  
Current Knowledge ◽  
Therapy Resistance ◽  
Success Rates ◽  
Common Cancer ◽  
And Migration

Breast cancer (BC ) is the most common cancer among women, and current treatments available often have high success rates. However, BC can acquire drug resistance and sometimes relapse. Current knowledge about the most aggressive forms of BC indicates the role of specific cells with stem properties located in BC, the so-called "BCSCs" (Brest cancer stem cells). The role of BCSCs in cancer formation, growth, invasiveness, therapy resistance, and tumor recurrence is becoming increasingly evident. The growth and metastatic properties of BCSCs are regulated in a variety of ways that are only partially known. Sex steroid receptors (SSRs), which are involved in the etiology and progression of BC, promote the proliferation, dedifferentiation and migration of BCSCs. However, the literature contains incomplete information about their roles. In particular, there are conflicting findings regarding the expression and role of classic BC hormone biomarkers such as estrogen receptor alpha (ERα), together with scanty, albeit promising, information on the properties of ER-beta (ERβ) and androgen receptor (AR) that control pathways of transduction in BCSC. In this review, we will discuss the role that SRs expressed in BCSCs play in BC progression and relapse, and how these findings have opened up new therapeutic options. These cells are predictors of BC and promising new therapies are being developed to target these cells and improve BC recurrence.

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