scholarly journals Ubiquitin-specific peptidase 37: an important cog in the oncogenic machinery of cancerous cells

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Ravi Chauhan ◽  
Ajaz A. Bhat ◽  
Tariq Masoodi ◽  
Puneet Bagga ◽  
Ravinder Reddy ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Posttranslational Modifications ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Therapeutics ◽  
Mesenchymal Transition ◽  
Protein Ubiquitination ◽  
Cancer Types ◽  
The Stability ◽  
Cancerous Cells

AbstractProtein ubiquitination is one of the most crucial posttranslational modifications responsible for regulating the stability and activity of proteins involved in homeostatic cellular function. Inconsistencies in the ubiquitination process may lead to tumorigenesis. Ubiquitin-specific peptidases are attractive therapeutic targets in different cancers and are being evaluated for clinical development. Ubiquitin-specific peptidase 37 (USP37) is one of the least studied members of the USP family. USP37 controls numerous aspects of oncogenesis, including stabilizing many different oncoproteins. Recent work highlights the role of USP37 in stimulating the epithelial-mesenchymal transition and metastasis in lung and breast cancer by stabilizing SNAI1 and stimulating the sonic hedgehog pathway, respectively. Several aspects of USP37 biology in cancer cells are yet unclear and are an active area of research. This review emphasizes the importance of USP37 in cancer and how identifying its molecular targets and signalling networks in various cancer types can help advance cancer therapeutics.

The Role of Calcium Signaling in Regulation of Epithelial-Mesenchymal Transition

2020 ◽  
pp. 1-23
Author(s):  
Divya Adiga ◽  
Raghu Radhakrishnan ◽  
Sanjiban Chakrabarty ◽  
Prashant Kumar ◽  
Shama Prasada Kabekkodu
Keyword(s):  
Cancer Metastasis ◽  
Epithelial To Mesenchymal Transition ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Cancer Therapeutics ◽  
Growth And Survival ◽  
Mesenchymal Transition ◽  
Microenvironmental Factors ◽  
Favorable Clinical Outcome

Despite substantial advances in the field of cancer therapeutics, metastasis is a significant challenge for a favorable clinical outcome. Epithelial to mesenchymal transition (EMT) is a process of acquiring increased motility, invasiveness, and therapeutic resistance by cancer cells for their sustained growth and survival. A plethora of intrinsic mechanisms and extrinsic microenvironmental factors drive the process of cancer metastasis. Calcium (Ca<sup>2+</sup>) signaling plays a critical role in dictating the adaptive metastatic cell behavior comprising of cell migration, invasion, angiogenesis, and intravasation. By modulating EMT, Ca<sup>2+</sup> signaling can regulate the complexity and dynamics of events leading to metastasis. This review summarizes the role of Ca<sup>2+</sup> signal remodeling in the regulation of EMT and metastasis in cancer.

scholarly journals Possible Role of Sonic Hedgehog and Epithelial-Mesenchymal Transition in Renal Cell Cancer Progression

2013 ◽  
Vol 54 (8) ◽  
pp. 547 ◽  
Author(s):  
Hosny M. Behnsawy ◽  
Katsumi Shigemura ◽  
Fatma Y. Meligy ◽  
Fukashi Yamamichi ◽  
Masuo Yamashita ◽  
...  
Keyword(s):  
Sonic Hedgehog ◽  
Cancer Progression ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cell Cancer ◽  
Mesenchymal Transition

scholarly journals Hepatitis B virus X protein promotes vimentin expression via LIM and SH3 domain protein 1 to facilitate epithelial-mesenchymal transition and hepatocarcinogenesis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongjuan You ◽  
Dongchen Yuan ◽  
Yanwei Bi ◽  
Ning Zhang ◽  
Qi Li ◽  
...  
Keyword(s):  
Western Blot ◽  
Epithelial Mesenchymal Transition ◽  
Hepatoma Cells ◽  
Signal Pathways ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
B Virus ◽  
And Migration ◽  
The Stability

Abstract Background Hepatitis B virus (HBV) X protein (HBX) has been reported to be responsible for the epithelial-mesenchymal transition (EMT) in HBV-related hepatocellular carcinoma (HCC). Vimentin is an EMT-related molecular marker. However, the importance of vimentin in the pathogenesis of HCC mediated by HBX has not been well determined. Methods The expression of vimentin induced by HBX, and the role of LIM and SH3 domain protein 1 (LASP1) in HBX-induced vimentin expression in hepatoma cells were examined by western blot and immunohistochemistry analysis. Both the signal pathways involved in the expression of vimentin, the interaction of HBX with vimentin and LASP1, and the stability of vimentin mediated by LASP1 in HBX-positive cells were assessed by western blot, Co-immunoprecipitation, and GST-pull down assay. The role of vimentin in EMT, proliferation, and migration of HCC cells mediated by HBX and LASP1 were explored with western blot, CCK-8 assay, plate clone formation assay, transwell assay, and wound healing assay. Results Vimentin expression was increased in both HBX-positive hepatoma cells and HBV-related HCC tissues, and the expression of vimentin was correlated with HBX in HBV-related HCC tissues. Functionally, vimentin was contributed to the EMT, proliferation, and migration of hepatoma cells mediated by HBX. The mechanistic analysis suggested that HBX was able to enhance the expression of vimentin through LASP1. On the one hand, PI3-K, ERK, and STAT3 signal pathways were involved in the upregulation of vimentin mediated by LASP1 in HBX-positive hepatoma cells. On the other hand, HBX could directly interact with vimentin and LASP1, and dependent on LASP1, HBX was capable of promoting the stability of vimentin via protecting it from ubiquitination mediated protein degradation. Besides these, vimentin was involved in the growth and migration of hepatoma cells mediated by LASP1 in HBX-positive hepatoma cells. Conclusion Taken together, these findings demonstrate that, dependent on LASP1, vimentin is crucial for HBX-mediated EMT and hepatocarcinogenesis, and may serve as a potential target for HBV-related HCC treatment.

scholarly journals Wnt Signaling Pathway Is among the Drivers of Liver Metastasis

Livers ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 180-200
Author(s):  
Ivana Samaržija
Keyword(s):  
Liver Metastasis ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Epithelial Mesenchymal Transition ◽  
Wnt Signaling Pathway ◽  
Metastasis Formation ◽  
Mesenchymal Transition ◽  
Cancer Types ◽  
The Many

Liver metastasis, originating either from a primary liver or other cancer types, represent a large cancer-related burden. Therefore, studies that add to better understanding of its molecular basis are needed. Herein, the role of the Wnt signaling pathway in liver metastasis is outlined. Its role in hepatocellular carcinoma (HCC) epithelial-mesenchymal transition (EMT), motility, migration, metastasis formation, and other steps of the metastatic cascade are presented. Additionally, the roles of the Wnt signaling pathway in the liver metastasis formation of colorectal, breast, gastric, lung, melanoma, pancreatic, and prostate cancer are explored. The special emphasis is given to the role of the Wnt signaling pathway in the communication between the many of the components of the primary and secondary cancer microenvironment that contribute to the metastatic outgrowth in the liver. The data presented herein are a review of the most recent publications and advances in the field that add to the idea that the Wnt pathway is among the drivers of liver metastasis and that its targeting could potentially relieve liver metastasis–related complications.

scholarly journals Pathomorphology of the carcinomas

2018 ◽  
Vol 74 (1) ◽  
pp. 5-15
Author(s):  
JANUSZ A. MADEJ
Keyword(s):  
Cell Line ◽  
Epithelial Mesenchymal Transition ◽  
Functional Differentiation ◽  
Mesenchymal Transition ◽  
Expression Of Genes ◽  
Cancer Types ◽  
Specific Antigens

The paper describes the morphological and functional differentiation of cancer cells and mentions basic markers combined with that phenomenon. Table 1 presents cariotypic and immunophenotypic changes, neoplastic biomarkers and biological products present within the cells in selected cancer types. The authors also present changes in the cell cycle that leads to cancerogenesis with an emphasis put on the role of so-called genome guardians, i.e. TP53 and RB1 genes, and describe the main epigenetic factors, including the DNA methylation process in CDH1 (cadherin1) gene. The article also shows the morphologic types of proliferative changes: pre-cancer lesions (laesio praecancerosus), pre-cancer states (status praecancerosus) and pre-invasive carcinoma (carcinoma praeinvasivum, carcinoma in situ). A new classification of carcinomas is presented, including tumours originating from: a – a luminal epithelial-like cell line (with typical epithelial markers – E-cadherin, desmoplakin 1), b – a weakly luminal epithelial-like cell line (with a visibly weakened expression of epithelial antigenes) and c – a mesenchymal-like cell line (with the presence of proteins typical for mesenchymal cells – vimentin, N-cadherin, and lack of epithelial-specific antigens). Moreover, the authors extensively describe the so-called epithelial mesenchymal transition (EMT) that can be observed both in in vitro and in vivo conditions. The role of cancer-associated fibroblasts (CAFs) in that process is shown. The cells exhibit an increase in the expression of genes involved in adhesion and angiogenesis and an increased expression of neurotransmitter receptors (adrenaline, noradrenaline)....

Magnesium Chloride is an Effective Therapeutic Agent for Prostate Cancer

2018 ◽  
Vol 8 (1) ◽  
pp. 62 ◽  
Author(s):  
Julianna Maria Santos ◽  
Fazle Hussain
Keyword(s):  
Prostate Cancer ◽  
Magnesium Chloride ◽  
Epithelial Mesenchymal Transition ◽  
Chromatin Condensation ◽  
Myosin Ii ◽  
In Vivo Studies ◽  
Migration Speed ◽  
Mesenchymal Transition

Background: Reduced levels of magnesium can cause several diseases and increase cancer risk. Motivated by magnesium chloride’s (MgCl2) non-toxicity, physiological importance, and beneficial clinical applications, we studied its action mechanism and possible mechanical, molecular, and physiological effects in prostate cancer with different metastatic potentials.Methods: We examined the effects of MgCl2, after 24 and 48 hours, on apoptosis, cell migration, expression of epithelial mesenchymal transition (EMT) markers, and V-H+-ATPase, myosin II (NMII) and the transcription factor NF Kappa B (NFkB) expressions.Results: MgCl2 induces apoptosis, and significantly decreases migration speed in cancer cells with different metastatic potentials.  MgCl2 reduces the expression of V-H+-ATPase and myosin II that facilitates invasion and metastasis, suppresses the expression of vimentin and increases expression of E-cadherin, suggesting a role of MgCl2 in reversing the EMT. MgCl2 also significantly increases the chromatin condensation and decreases NFkB expression.Conclusions: These results suggest a promising preventive and therapeutic role of MgCl2 for prostate cancer. Further studies should explore extending MgCl2 therapy to in vivo studies and other cancer types.Keywords: Magnesium chloride, prostate cancer, migration speed, V-H+-ATPase, and EMT.

Effect of Annexins Translocated in Extracellular Vesicles on Tumorigenesis

2020 ◽  
Vol 20 ◽  
Author(s):  
Qionghui Wu ◽  
Haidong Wei ◽  
Wenbo Meng ◽  
Xiaodong Xie ◽  
Zhenchang Zhang ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cell ◽  
Epithelial Mesenchymal Transition ◽  
Main Role ◽  
Tumor Cell Adhesion ◽  
Mesenchymal Transition ◽  
Calcium Dependent ◽  
Tumor Neovascularization

: Annexin, a calcium-dependent phospholipid binding protein, can affect tumor cell adhesion, proliferation, apoptosis, invasion and metastasis, as well as tumor neovascularization in different ways. Recent studies have shown that annexin exists not only as an intracellular protein in tumor cells, but also in different ways to be secret outside the cell as a “crosstalk” tool for tumor cells and tumor microenvironment, thus playing an important role in the development of tumors, such as participating in epithelial-mesenchymal transition, regulating immune cell behavior, promoting neovascularization and so on. The mechanism of annexin secretion in the form of extracellular vesicles and its specific role is still unclear. This paper summarizes the main role of annexin secreted into the extracellular space in the form of extracellular vesicles in tumorigenesis and drug resistance and analyzes its possible mechanism.

scholarly journals Correction to: The role of epithelial–mesenchymal transition (EMT)-associated genes during gonadogenesis of albino rat

2020 ◽  
Vol 81 (1) ◽  
Author(s):  
Lina A. Aeshra ◽  
Maiada Moustafa ◽  
Mohammed I. Y. Elmallah ◽  
Said Abdelrahman Salih ◽  
Ibrahim Y. Abdel Kader
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Albino Rat ◽  
Mesenchymal Transition
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