scholarly journals The function of the co-chaperone ERdj4 in diverse (patho-)physiological conditions

2021 ◽  
Vol 79 (1) ◽  
Author(s):  
Lea Daverkausen-Fischer ◽  
Felicitas Pröls
Keyword(s):  
Cellular Response ◽  
Epithelial To Mesenchymal Transition ◽  
Physiological State ◽  
Tumor Development ◽  
Degradation Pathway ◽  
Cellular Protein ◽  
Misfolded Proteins ◽  
Human Stem Cells ◽  
Central Process ◽  
Mesenchymal Transition

AbstractAccumulation of misfolded proteins in the endoplasmic reticulum (ER) induces a well-orchestrated cellular response to reduce the protein burden within the ER. This unfolded protein response (UPR) is controlled primarily by three transmembrane proteins, IRE1α, ATF6, and PERK, the activity of which is controlled by BiP, the ER-resident Hsp70 protein. Binding of BiP to co-chaperones via their highly conserved J-domains stimulates the intrinsic ATPase activity of BiP, thereby providing the energy necessary for (re-)folding of proteins, or for targeting of misfolded proteins to the degradation pathway, processes specified and controlled by the respective co-chaperone. In this review, our aim is to elucidate the function of the co-chaperone ERDJ4, also known as MDG1, MDJ7, or DNAJB9. Knockout and knockin experiments clearly point to the central role of ERDJ4 in controlling lipogenesis and protein synthesis by promoting degradation of SREBP1c and the assembly of the protein complex mTORC2. Accumulating data reveal that ERDJ4 controls epithelial-to-mesenchymal transition, a central process during embryogenesis, in wound healing, and tumor development. Overexpression of ERdj4 has been shown to improve engraftment of transplanted human stem cells, possibly due to its ability to promote cellular survival in stressed cells. High ERDJ4-plasma levels are specific for fibrillary glomerulonephritis and serve as a diagnostic marker. As outlined in this review, the functions of ERDJ4 are manifold, depending on the cellular (patho-) physiological state, the cellular protein repertoire, and the subcellular localization of ERDJ4.

scholarly journals CXCL12 and Its Isoforms: Different Roles in Pancreatic Cancer?

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandra Righetti ◽  
Matteo Giulietti ◽  
Berina Šabanović ◽  
Giulia Occhipinti ◽  
Giovanni Principato ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Microenvironment ◽  
Stromal Cells ◽  
Tumor Invasion ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Tumor Development ◽  
Physiological Role ◽  
Mesenchymal Transition ◽  
Splicing Isoforms

CXCL12 is a chemokine that acts through CXCR4 and ACKR3 receptors and plays a physiological role in embryogenesis and haematopoiesis. It has an important role also in tumor development, since it is released by stromal cells of tumor microenvironment and alters the behavior of cancer cells. Many studies investigated the roles of CXCL12 in order to understand if it has an anti- or protumor role. In particular, it seems to promote tumor invasion, proliferation, angiogenesis, epithelial to mesenchymal transition (EMT), and metastasis in pancreatic cancer. Nevertheless, some evidence shows opposite functions; therefore research on CXCL12 is still ongoing. These discrepancies could be due to the presence of at least six CXCL12 splicing isoforms, each with different roles. Interestingly, three out of six variants have the highest levels of expression in the pancreas. Here, we report the current knowledge about the functions of this chemokine and then focus on pancreatic cancer. Moreover, we discuss the methods applied in recent studies in order to understand if they took into account the existence of the CXCL12 isoforms.

scholarly journals Lamins in Lung Cancer: Biomarkers and Key Factors for Disease Progression through miR-9 Regulation?

Cells ◽  
2018 ◽  
Vol 7 (7) ◽  
pp. 78 ◽  
Author(s):  
Julien Guinde ◽  
Diane Frankel ◽  
Sophie Perrin ◽  
Valérie Delecourt ◽  
Nicolas Lévy ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Nuclear Lamina ◽  
Metastatic Potential ◽  
Disease Diagnosis ◽  
Carcinoma Cells ◽  
Scaffolding Protein ◽  
Mesenchymal Transition ◽  
Cancer Subtypes

Lung cancer represents the primary cause of cancer death in the world. Malignant cells identification and characterization are crucial for the diagnosis and management of patients with primary or metastatic cancers. In this context, the identification of new biomarkers is essential to improve the differential diagnosis between cancer subtypes, to select the most appropriate therapy, and to establish prognostic correlations. Nuclear abnormalities are hallmarks of carcinoma cells and are used as cytological diagnostic criteria of malignancy. Lamins (divided into A- and B-types) are localized in the nuclear matrix comprising nuclear lamina, where they act as scaffolding protein, involved in many nuclear functions, with regulatory effects on the cell cycle and differentiation, senescence and apoptosis. Previous studies have suggested that lamins are involved in tumor development and progression with opposite results concerning their prognostic role. This review provides an overview of lamins expression in lung cancer and the relevance of these findings for disease diagnosis and prognosis. Furthermore, we discuss the link between A-type lamins expression in lung carcinoma cells and nuclear deformability, epithelial to mesenchymal transition, and metastatic potential, and which mechanisms could regulate A-type lamins expression in lung cancer, such as the microRNA miR-9.

scholarly journals Cathepsin B Is Upregulated and Mediates ECM Degradation in Colon Adenocarcinoma HT29 Cells Overexpressing Snail

Cells ◽  
2019 ◽  
Vol 8 (3) ◽  
pp. 203 ◽  
Author(s):  
Jakub Kryczka ◽  
Izabela Papiewska-Pajak ◽  
M. Anna Kowalska ◽  
Joanna Boncela
Keyword(s):  
Cathepsin B ◽  
Epithelial To Mesenchymal Transition ◽  
Early Stage ◽  
Tumor Development ◽  
Colon Adenocarcinoma ◽  
Mesenchymal Cell ◽  
Tissue Samples ◽  
Mesenchymal Transition ◽  
Colon And Rectum ◽  
Phenotypic Shift

During tumor development and ongoing metastasis the acquisition of mesenchymal cell traits by epithelial carcinoma cells is achieved through a programmed phenotypic shift called the epithelial-to-mesenchymal transition, EMT. EMT contributes to increased cancer cell motility and invasiveness mainly through invadosomes, the adhesion structures that accompany the mesenchymal migration. The invadosomes and their associated proteases restrict protease activity to areas of the cell in direct contact with the ECM, thus precisely controlling cell invasion. Our data prove that Snail-overexpressing HT-29 cells that imitate the phenotype of colon cancer cells in the early stage of the EMT showed an increase in the expression and pericellular activity of cathepsin B. It appears that the pericellular localization of cathepsin B, also observed in colon and rectum adenocarcinoma tissue samples, plays a key role in its function.

Short-term effect of FSH on gene expression in bovine granulosa cells in vitro

2018 ◽  
Vol 30 (8) ◽  
pp. 1154 ◽  
Author(s):  
Anne-Laure Nivet ◽  
Isabelle Dufort ◽  
Isabelle Gilbert ◽  
Marc-André Sirard
Keyword(s):  
Gene Expression ◽  
Cellular Response ◽  
Epithelial To Mesenchymal Transition ◽  
Short Term ◽  
Mesenchymal Transition ◽  
Vitro Model ◽  
Cell Transcriptome ◽  
Physical Changes

In reproduction, FSH is one of the most important hormones, especially in females, because it controls the number of follicles and the rate of follicular growth. Although several studies have examined the follicular response at the transcriptome level, it is difficult to obtain a clear and complete picture of the genes responding to an increase in FSH in an in vivo context because follicles undergo rapid morphological and physical changes during their growth. To help define the transcriptome downstream response to FSH, an in vitro model was used in the present study to observe the short-term (4 h) cellular response. Gene expression analysis highlighted a set of novel transcripts that had not been reported previously as being part of the FSH response. Moreover, the results of the present study indicate that the epithelial to mesenchymal transition pathway is inhibited by short-term FSH stimuli, maintaining follicles in a growth phase and preventing differentiation. Modulating gene expression in vitro has physiological limitations, but it can help assess the potential downstream response and begin the mapping of the granulosa cell transcriptome in relation to FSH. This information is a key feature to help discriminate between the effects of FSH and LH, or to elucidate the overlapping of insulin-like growth factor 1 and FSH in the granulosa mitogenic response.

scholarly journals Isoliquiritigenin Inhibits Ovarian Cancer Metastasis by Reversing Epithelial-to-Mesenchymal Transition

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3725 ◽  
Author(s):  
Chen Chen ◽  
Shuang Huang ◽  
Chang-Liang Chen ◽  
Sing-Bing Su ◽  
Dong-Dong Fang
Keyword(s):  
Ovarian Cancer ◽  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Skov3 Cell ◽  
Anticancer Activities ◽  
Mesenchymal Transition ◽  
Epithelial Phenotype ◽  
Ovary Tumor

The epithelial-to-mesenchymal transition (EMT) plays a prominent role in cancer metastasis. Isoliquiritigenin (ISL), one of the flavonoids in licorice, has been shown to exhibit anticancer activities in many cancer types through various mechanisms. However, it is unknown whether ISL impacts the EMT process. Here, we show that ISL is able to suppress mesenchymal features of ovarian cancer SKOV3 and OVCAR5 cells, evidenced by an apparent morphological change from a mesenchymal to an epithelial phenotype and reduced levels of mesenchymal markers accompanied by the gain of E-cadherin expression. The suppression of EMT is also supported by the observed decrease in cell migration and in vitro invasion upon ISL treatment. Moreover, we show that ISL effectively blocks the intraperitoneal xenograft development of the SKOV3 cell line and prolonged the survival of tumor-bearing mice. These data suggest that ISL inhibits intraperitoneal ovary tumor development through the suppression of EMT, indicating that ISL may be an effective therapeutic agent against ovarian cancer.

scholarly journals BRCA1 Suppresses Epithelial-to-Mesenchymal Transition and Stem Cell Dedifferentiation during Mammary and Tumor Development

2014 ◽  
Vol 74 (21) ◽  
pp. 6161-6172 ◽  
Author(s):  
Feng Bai ◽  
Ho Lam Chan ◽  
Alexandria Scott ◽  
Matthew D. Smith ◽  
Cheng Fan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Cell Dedifferentiation ◽  
Mesenchymal Transition

scholarly journals Expression of POU2F3 Transcription Factor Control Inflammation, Immunological Recruitment and Metastasis of Pancreatic Cancer in Mice

Biology ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 341
Author(s):  
Jennifer Bintz ◽  
Analía Meilerman Abuelafia ◽  
François Gerbe ◽  
Elodie Baudoin ◽  
Nathalie Auphan-Anezin ◽  
...  
Keyword(s):  
Animal Model ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Inflammatory Cells ◽  
Mice Model ◽  
Mesenchymal Transition ◽  
Inflammatory Microenvironment ◽  
Tuft Cells ◽  
Deficient Mice

TUFT cells have been described as strong modulators of inflammatory cells in several tissues including pancreas. TUFT cells, also known as DCLK1+ cells, are dependent of the transcriptional factor POU2F3. Several works report DCLK1+ cells in early stages of PDAC development suggesting an important role of TUFT cells in PDAC development. Therefore, we developed a mice model (PDX1-Cre;KrasG12D;Ink4afl/fl), known as PKI model, deficient or not of POU2F3. In this animal model, deficiency of POU2F3 results in the absence of TUFT cells in PDAC as expected. Although, tumor development and growth are not significantly influenced, the development of liver metastasis was almost completely inhibited in POU2F3-deficient mice. Surprisingly, the absence of metastasis was associated with a higher expression of epithelial-to-mesenchymal transition markers, but to a lower inflammatory microenvironment suggesting that inflammation influences metastasis production more than epithelial-to-mesenchymal transition in this animal model. We can conclude that POU2F3 could be a new therapeutic target for control PDAC progression.

scholarly journals Notch Signaling Function in the Angiocrine Regulation of Tumor Development

Cells ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 2467
Author(s):  
Alexandre Trindade ◽  
António Duarte
Keyword(s):  
Endothelial Cells ◽  
Notch Signaling ◽  
Tumor Angiogenesis ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Development ◽  
Blood Perfusion ◽  
Notch Signaling Pathway ◽  
Mesenchymal Transition ◽  
Solid Malignancies ◽  
Signaling Function

The concept of tumor growth being angiogenesis dependent had its origin in the observations of Judah Folkman in 1969 of a retinoblastoma in a child. Tumor angiogenesis is initiated when endothelial cells (ECs) respond to local stimuli and migrate towards the growing mass, which results in the formation of tubular structures surrounded by perivascular support cells that transport blood to the inner tumor. In turn, the neo-vasculature supports tumor development and eventual metastasis. This process is highly regulated by several signaling pathways. Central to this process is the Notch signaling pathway. Beyond the role of Notch signaling in tumor angiogenesis, a major hallmark of cancer development, it has also been implicated in the regulation of tumor cell proliferation and survival, in epithelial-to-mesenchymal transition, invasion and metastasis and in the regulation of cancer stem cells, in a variety of hematologic and solid malignancies. There is increasing evidence for the tumor vasculature being important in roles other than those linked to blood perfusion. Namely, endothelial cells act on and influence neighboring tumor cells by use of angiocrine factors to generate a unique cellular microenvironment, thereby regulating tumor stem-like cells’ homeostasis, modulating tumor progression, invasiveness, trafficking and metastasis. This review will focus on Notch signaling components that play a part in angiocrine signaling in a tumor setting.

scholarly journals Emerging Roles of DDB2 in Cancer

2019 ◽  
Vol 20 (20) ◽  
pp. 5168 ◽  
Author(s):  
Pauline Gilson ◽  
Guillaume Drouot ◽  
Andréa Witz ◽  
Jean-Louis Merlin ◽  
Philippe Becuwe ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Excision Repair ◽  
Biological Effects ◽  
Cell Formation ◽  
Tumor Development ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Clinical Consequences ◽  
Cycle Regulation

Damage-specific DNA-binding protein 2 (DDB2) was originally identified as a DNA damage recognition factor that facilitates global genomic nucleotide excision repair (GG-NER) in human cells. DDB2 also contributes to other essential biological processes such as chromatin remodeling, gene transcription, cell cycle regulation, and protein decay. Recently, the potential of DDB2 in the development and progression of various cancers has been described. DDB2 activity occurs at several stages of carcinogenesis including cancer cell proliferation, survival, epithelial to mesenchymal transition, migration and invasion, angiogenesis, and cancer stem cell formation. In this review, we focus on the current state of scientific knowledge regarding DDB2 biological effects in tumor development and the underlying molecular mechanisms. We also provide insights into the clinical consequences of DDB2 activity in cancers.

scholarly journals Targeting the Epithelial-to-Mesenchymal Transition in Cancer Stem Cells for a Better Clinical Outcome of Glioma

2020 ◽  
Vol 19 ◽  
pp. 153303382094805
Author(s):  
Yu-bao Lu ◽  
Tian-Jiao Sun ◽  
Yu-tong Chen ◽  
Zong-Yan Cai ◽  
Jia-Yu Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Tumor Therapy ◽  
Tumor Development ◽  
Mesenchymal Transition ◽  
Important Target ◽  
The Central Nervous System

Glioma is one of the most common malignant tumors of the central nervous system with a poor prognosis at present due to lack of effective treatment options. Its initiation, migration, and multipotency are affected by cancer stem cell’s transition. Previous studies imply that changes in the cancer stem cells can affect the malignant differentiation of the tumor. We found that the epithelial-to-mesenchymal transition (EMT)-related regulatory pathway is an important target for tumor therapy. In this review, we discuss the transition factor of EMT and 3 specific pathways that affect the EMT of cancer stem cells during tumor development. We conclude that targeting the EMT process of cancer stem cells can be a feasible approach in the treatment of glioma.

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