The Experts below are selected from a list of 16146 Experts worldwide ranked by ideXlab platform
Zhiwei Wang - One of the best experts on this subject based on the ideXlab platform.
-
regulation of emt by Notch Signaling Pathway in tumor progression
Current Cancer Drug Targets, 2013Co-Authors: Xiujuan Qian, Jun Xia, Lucio Miele, Fazlul H Sarkar, Zhiwei WangAbstract:Notch Signaling Pathway has been reported to play critical roles in the development and progression of human cancers because Notch Signaling Pathway is critically involved in many cellular processes including cell proliferation, survival, apoptosis, migration, invasion, angiogenesis, and metastasis. Emerging evidence suggests that Notch regulates EMT (Epithelial-to-Mesenchymal Transition), leading to tumor invasion and metastasis. Thus, this mini-review is focused on discussing the novel role of Notch Signaling Pathway in the regulation of EMT. Moreover, we summarized that Notch Signaling Pathway could be down-regulated by its inhibitors or natural compounds, resulting in the reversal of EMT to MET (Mesenchymal-to-Epithelial Transition), which could be a promising strategy for achieving better treatment outcome in patients diagnosed with cancer.
-
targeting Notch Signaling Pathway to overcome drug resistance for cancer therapy
Biochimica et Biophysica Acta, 2010Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Aamir Ahmad, Asfar S Azmi, Fazlul H SarkarAbstract:Chemotherapy is an important therapeutic strategy for cancer treatment and remains the mainstay for the management of human malignancies; however, chemotherapy fails to eliminate all tumor cells because of intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Recently, emerging evidences suggest that Notch Signaling Pathway is one of the most important Signaling Pathways in drug-resistant tumor cells. Moreover, down-regulation of Notch Pathway could induce drug sensitivity, leading to increased inhibition of cancer cell growth, invasion, and metastasis. This article will provide a brief overview of the published evidences in support of the roles of Notch in drug resistance and will further summarize how targeting Notch by "natural agents" could become a novel and safer approach for the improvement of tumor treatment by overcoming drug resistance.
-
Notch Signaling proteins legitimate targets for cancer therapy
Current Protein & Peptide Science, 2010Co-Authors: Zhiwei Wang, Fazlul H SarkarAbstract:Proteins and small peptides (growth factors and hormones) are key molecules in maintaining cellular homeostasis. To that end, Notch Signaling Pathway proteins are known to play critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thus it has been suggested that Notch may be responsible for the development and progression of human malignancies. Therefore, the Notch Signaling Pathway proteins may present novel therapeutic targets, which could have promising therapeutic impact on eradicating human malignancies. This review describes the role of Notch Signaling Pathway proteins in cancer and how its deregulation is involved in tumor development and progression leading to metastasis and the ultimate demise of patients diagnosed with cancer. Further, we summarize the role of several Notch inhibitors especially “natural agents” that could represent novel therapeutic strategies targeting Notch Signaling toward better treatment outcome of patients diagnosed with cancer.
-
the role of Notch Signaling Pathway in epithelial mesenchymal transition emt during development and tumor aggressiveness
Current Drug Targets, 2010Co-Authors: Zhiwei Wang, Dejuan Kong, Fazlul H SarkarAbstract:The Notch Signaling Pathway maintains a balance between cell proliferation and apoptosis, and thus it is believed that Notch Signaling Pathway may play an important role in the development and progression of several malignancies. However, the functions of Notch Signaling in EMT are largely unknown. This mini review describes the role of Notch Signaling Pathway in EMT, and cataloging how its deregulation is involved in EMT and tumor aggressiveness. Further attempts have been made to summarize the role of several chemopreventive agents that could be useful for targeted inactivation of Notch Signaling, and thus it may cause reversal of EMT, which could become a novel approach for cancer prevention and treatment.
-
acquisition of epithelial mesenchymal transition phenotype of gemcitabine resistant pancreatic cancer cells is linked with activation of the Notch Signaling Pathway
Cancer Research, 2009Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Aamir Ahmad, Asfar S Azmi, Shadan Ali, James L Abbruzzese, Gary E Gallick, Fazlul H SarkarAbstract:Despite rapid advances in many fronts, pancreatic cancer (PC) remains one of the most difficult human malignancies to treat due, in part, to de novo and acquired chemoresistance and radioresistance. Gemcitabine alone or in combination with other conventional therapeutics is the standard of care for the treatment of advanced PC without any significant improvement in the overall survival of patients diagnosed with this deadly disease. Previous studies have shown that PC cells that are gemcitabine-resistant (GR) acquired epithelial-mesenchymal transition (EMT) phenotype, which is reminiscent of "cancer stem-like cells"; however, the molecular mechanism that led to EMT phenotype has not been fully investigated. The present study shows that Notch-2 and its ligand, Jagged-1, are highly up-regulated in GR cells, which is consistent with the role of the Notch Signaling Pathway in the acquisition of EMT and cancer stem-like cell phenotype. We also found that the down-regulation of Notch Signaling was associated with decreased invasive behavior of GR cells. Moreover, down-regulation of Notch Signaling by siRNA approach led to partial reversal of the EMT phenotype, resulting in the mesenchymal-epithelial transition, which was associated with decreased expression of vimentin, ZEB1, Slug, Snail, and nuclear factor-kappaB. These results provide molecular evidence showing that the activation of Notch Signaling is mechanistically linked with chemoresistance phenotype (EMT phenotype) of PC cells, suggesting that the inactivation of Notch Signaling by novel strategies could be a potential targeted therapeutic approach for overcoming chemoresistance toward the prevention of tumor progression and/or treatment of metastatic PC.
Fazlul H Sarkar - One of the best experts on this subject based on the ideXlab platform.
-
regulation of emt by Notch Signaling Pathway in tumor progression
Current Cancer Drug Targets, 2013Co-Authors: Xiujuan Qian, Jun Xia, Lucio Miele, Fazlul H Sarkar, Zhiwei WangAbstract:Notch Signaling Pathway has been reported to play critical roles in the development and progression of human cancers because Notch Signaling Pathway is critically involved in many cellular processes including cell proliferation, survival, apoptosis, migration, invasion, angiogenesis, and metastasis. Emerging evidence suggests that Notch regulates EMT (Epithelial-to-Mesenchymal Transition), leading to tumor invasion and metastasis. Thus, this mini-review is focused on discussing the novel role of Notch Signaling Pathway in the regulation of EMT. Moreover, we summarized that Notch Signaling Pathway could be down-regulated by its inhibitors or natural compounds, resulting in the reversal of EMT to MET (Mesenchymal-to-Epithelial Transition), which could be a promising strategy for achieving better treatment outcome in patients diagnosed with cancer.
-
targeting Notch Signaling Pathway to overcome drug resistance for cancer therapy
Biochimica et Biophysica Acta, 2010Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Aamir Ahmad, Asfar S Azmi, Fazlul H SarkarAbstract:Chemotherapy is an important therapeutic strategy for cancer treatment and remains the mainstay for the management of human malignancies; however, chemotherapy fails to eliminate all tumor cells because of intrinsic or acquired drug resistance, which is the most common cause of tumor recurrence. Recently, emerging evidences suggest that Notch Signaling Pathway is one of the most important Signaling Pathways in drug-resistant tumor cells. Moreover, down-regulation of Notch Pathway could induce drug sensitivity, leading to increased inhibition of cancer cell growth, invasion, and metastasis. This article will provide a brief overview of the published evidences in support of the roles of Notch in drug resistance and will further summarize how targeting Notch by "natural agents" could become a novel and safer approach for the improvement of tumor treatment by overcoming drug resistance.
-
Notch Signaling proteins legitimate targets for cancer therapy
Current Protein & Peptide Science, 2010Co-Authors: Zhiwei Wang, Fazlul H SarkarAbstract:Proteins and small peptides (growth factors and hormones) are key molecules in maintaining cellular homeostasis. To that end, Notch Signaling Pathway proteins are known to play critical roles in maintaining the balance between cell proliferation, differentiation and apoptosis, and thus it has been suggested that Notch may be responsible for the development and progression of human malignancies. Therefore, the Notch Signaling Pathway proteins may present novel therapeutic targets, which could have promising therapeutic impact on eradicating human malignancies. This review describes the role of Notch Signaling Pathway proteins in cancer and how its deregulation is involved in tumor development and progression leading to metastasis and the ultimate demise of patients diagnosed with cancer. Further, we summarize the role of several Notch inhibitors especially “natural agents” that could represent novel therapeutic strategies targeting Notch Signaling toward better treatment outcome of patients diagnosed with cancer.
-
the role of Notch Signaling Pathway in epithelial mesenchymal transition emt during development and tumor aggressiveness
Current Drug Targets, 2010Co-Authors: Zhiwei Wang, Dejuan Kong, Fazlul H SarkarAbstract:The Notch Signaling Pathway maintains a balance between cell proliferation and apoptosis, and thus it is believed that Notch Signaling Pathway may play an important role in the development and progression of several malignancies. However, the functions of Notch Signaling in EMT are largely unknown. This mini review describes the role of Notch Signaling Pathway in EMT, and cataloging how its deregulation is involved in EMT and tumor aggressiveness. Further attempts have been made to summarize the role of several chemopreventive agents that could be useful for targeted inactivation of Notch Signaling, and thus it may cause reversal of EMT, which could become a novel approach for cancer prevention and treatment.
-
acquisition of epithelial mesenchymal transition phenotype of gemcitabine resistant pancreatic cancer cells is linked with activation of the Notch Signaling Pathway
Cancer Research, 2009Co-Authors: Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Aamir Ahmad, Asfar S Azmi, Shadan Ali, James L Abbruzzese, Gary E Gallick, Fazlul H SarkarAbstract:Despite rapid advances in many fronts, pancreatic cancer (PC) remains one of the most difficult human malignancies to treat due, in part, to de novo and acquired chemoresistance and radioresistance. Gemcitabine alone or in combination with other conventional therapeutics is the standard of care for the treatment of advanced PC without any significant improvement in the overall survival of patients diagnosed with this deadly disease. Previous studies have shown that PC cells that are gemcitabine-resistant (GR) acquired epithelial-mesenchymal transition (EMT) phenotype, which is reminiscent of "cancer stem-like cells"; however, the molecular mechanism that led to EMT phenotype has not been fully investigated. The present study shows that Notch-2 and its ligand, Jagged-1, are highly up-regulated in GR cells, which is consistent with the role of the Notch Signaling Pathway in the acquisition of EMT and cancer stem-like cell phenotype. We also found that the down-regulation of Notch Signaling was associated with decreased invasive behavior of GR cells. Moreover, down-regulation of Notch Signaling by siRNA approach led to partial reversal of the EMT phenotype, resulting in the mesenchymal-epithelial transition, which was associated with decreased expression of vimentin, ZEB1, Slug, Snail, and nuclear factor-kappaB. These results provide molecular evidence showing that the activation of Notch Signaling is mechanistically linked with chemoresistance phenotype (EMT phenotype) of PC cells, suggesting that the inactivation of Notch Signaling by novel strategies could be a potential targeted therapeutic approach for overcoming chemoresistance toward the prevention of tumor progression and/or treatment of metastatic PC.
Mohammad Mahdi Forghanifard - One of the best experts on this subject based on the ideXlab platform.
-
SOX2/SALL4 stemness axis modulates Notch Signaling genes to maintain self-renewal capacity of esophageal squamous cell carcinoma
Molecular and Cellular Biochemistry, 2020Co-Authors: Mohammad Mahdi Forghanifard, Paniz Kasebi, Mohammad Reza AbbaszadeganAbstract:Stemness phenotype is considered as the centerpiece of cancer biology due to its potential in conventional chemo-radiotherapy resistance and tumor recurrence after clinical intervention. This feature in tumor mass belongs to activation of core regulatory stemness factors and different cell Signaling Pathways in cancer stem cells. We aimed in this study to elucidate contribution of Notch Signaling Pathway in stemness state of esophageal squamous cell carcinoma (ESCC) through their relevance with stem cell markers SOX2 and SALL4. 50 ESCC tumor and related margin normal tissues were considered and categorized based on SOX2/SALL4 expression pattern, and mRNA levels of Notch Signaling genes including ligands, receptors, target genes, and transcriptional coactivator were analyzed in the selected groups using qRT-PCR. Concomitant overexpression of stem cell markers SOX2 and SALL4 in ESCCs upregulated the involved genes in Notch Signaling Pathway. Upregulation of Notch Pathway genes associated with depth of tumor invasion and lymph node metastasis of ESCC. Based on biological function of SOX2 and SALL4 axis in stemness state potential, our results may suggest contribution of Notch Signaling Pathway in self-renewal capacity of ESCCs, as well as invasion and metastasis of the disease. To the best of our knowledge, this is the first report elucidating the crosstalk between SOX2/SALL4 stemness factors and Notch Signaling Pathway in cancer research.
-
TWIST1 correlates with Notch Signaling Pathway to develop esophageal squamous cell carcinoma
Molecular and Cellular Biochemistry, 2020Co-Authors: Yasaman Fahim, Mozhgan Yousefi, Mohammad Hossein Izadpanah, Mohammad Mahdi ForghanifardAbstract:Notch Signaling Pathway mediates different biological processes including stem cell self-renewal, progenitor cell fate decision, and terminal differentiation. TWIST1 plays a key role in tumor development and metastasis through inducing epithelial-mesenchymal transition (EMT). Expression of the core transcriptional complex of Notch Pathway and its target genes, as well as TWIST1 overexpression, are closely related to the aggressive clinicopathological variables of esophageal squamous cell carcinoma (ESCC). Here we aimed to functionally elucidate probable crosstalk between TWIST1 and Notch Pathway in ESCCs. Correlation between TWIST1 and Notch target genes was analyzed in 50 ESCCs and corresponding normal tissues. Using retroviral system, enforced expression of TWIST1 was established in ESCC line KYSE-30 cells and expression of Notch Signaling genes was assessed. Significant correlation between TWIST1 and HEY1/HEY2 expression was found in different pathological variable of ESCC poor prognosis. Induced expression of TWIST1 in KYSE-30 cells caused a noteworthy increase of Notch Pathway genes expression revealing regulatory role of TWIST1 on Notch Signaling genes in the cells. Based on existed correlations between expression of TWIST1 and Notch Pathway genes in different pathological features of ESCC patients, as well as KYSE-30 cell line, we may extrapolate that TWIST1 is involved in aggressiveness of the disease through regulation of Notch Signaling genes. To the best of knowledge, this is the first report describing the impact of TWIST1 on Notch cascade genes in ESCC.
Michael Chopp - One of the best experts on this subject based on the ideXlab platform.
-
microrna profiling in subventricular zone after stroke mir 124a regulates proliferation of neural progenitor cells through Notch Signaling Pathway
PLOS ONE, 2011Co-Authors: Xian Shuang Liu, Michael Chopp, Rui Lan Zhang, Tang Tao, Xin Li Wang, Haifa Kassis, Ann Hozeskasolgot, Li Zhang, Charles ChenAbstract:Background The Notch Signaling Pathway regulates adult neurogenesis under physiological and pathophysiological conditions. MicroRNAs are small non-coding RNA molecules that regulate gene expression. The present study investigated the effect of miR-124a on the Notch Signaling Pathway in stroke-induced neurogenesis. Methodology and Principal Findings We found that adult rats subjected to focal cerebral ischemia exhibited substantial reduction of miR-124a expression, a neuron specific miRNA, in the neural progenitor cells of the subventricular zone (SVZ) of the lateral ventricle, which was inversely associated with activation of Notch signals. In vitro, transfection of neural progenitor cells harvested from the SVZ of adult rat with miR-124a repressed Jagged-1 (JAG1), a ligand of Notch, in a luciferase construct containing the JAG1 target site. Introduction of miR-124a in neural progenitor cells significantly reduced JAG1 transcript and protein levels, leading to inactivation of Notch signals. Transfection of neural progenitor cells with miR-124a significantly reduced progenitor cell proliferation and promoted neuronal differentiation measured by an increase in the number of Doublecortin positive cells, a marker of neuroblasts. Furthermore, introduction of miR-124a significantly increased p27Kip1 mRNA and protein levels, a downstream target gene of the Notch Signaling Pathway. Conclusions Collectively, our study demonstrated that in vivo, stroke alters miRNA expression in SVZ neural progenitor cells and that in vitro, miR-124a mediates stroke-induced neurogenesis by targeting the JAG-Notch Signaling Pathway.
-
simvastatin enhances bone marrow stromal cell differentiation into endothelial cells via Notch Signaling Pathway
American Journal of Physiology-cell Physiology, 2009Co-Authors: Xinfeng Liu, Jieli Chen, Alex Zacharek, Xu Cui, Smita Savantbhonsale, Zhenguo Liu, Michael ChoppAbstract:Bone marrow stromal cells (BMSCs) are capable of differentiating into multiple cell lineages including endothelial cells. Simvastatin, an HMG-CoA reductase inhibitor that is used as a cholesterol-lowering agent, promotes endothelial differentiation from epithelial progenitor cells (EPC). The Notch Signaling Pathway, which plays a key role in multiple cell functions such as differentiation, proliferation, and apoptosis, can be regulated by simvastatin. Therefore, we examined the effect of simvastatin on BMSC differentiation into endothelial cells and the underlying mechanisms involved in this process. We observed that simvastatin stimulation of rat BMSCs resulted in significantly increased expression of endothelial-specific genes and proteins, including von Willebrand factor (vWF), CD31, vascular endothelial-cadherin (VE-cadherin), vascular endothelial growth factor receptor-2 (VEGFR2, Flk-1), and VEGF receptor 1 (VEGFR-1, Flt-1). Simvastatin also significantly increased capillary tubelike formation of the BMSCs. In addition, the intracellular cleavage of Notch (NICD) was markedly enhanced by simvastatin in BMSCs. Incubation of BMSCs with a γ-secretase inhibitor, or Notch1 small interfering RNA (siRNA) that significantly inhibited the formation of NICD, blocked the expression of endothelial-specific markers in BMSCs and their differentiation into functional endothelial cells. These data suggest that simvastatin induces rat BMSCs differentiation into endothelial cells via a Notch Signaling Pathway.
S K Saha - One of the best experts on this subject based on the ideXlab platform.
-
KRT19 directly interacts with β-catenin/RAC1 complex to regulate NUMB-dependent Notch Signaling Pathway and breast cancer properties
Oncogene, 2017Co-Authors: S K Saha, H Y Choi, A A Dayem, G-m YangAbstract:Studies have reported that interactions between keratins (KRTs) and other proteins initiate Signaling cascades that regulate cell migration, invasion, and metastasis. In the current study, we found that expression of KRT19 was specifically high in breast cancers and significantly correlated with their invasiveness. Moreover, knockdown of KRT19 led to increased proliferation, migration, invasion, drug resistance, and sphere formation in breast cancer cells via an upregulated Notch Signaling Pathway. This was owing to reduced expression of NUMB, an inhibitory protein of the Notch Signaling Pathway. In addition, we found that KRT19 interacts with β-catenin/RAC1 complex and enhances the nuclear translocation of β-catenin. Concordantly, knockdown of KRT19 suppressed the nuclear translocation of β-catenin as well as β-catenin-mediated NUMB expression. Furthermore, modulation of KRT19-mediated regulation of NUMB and Notch1 expression led to the repression of the cancer stem cell properties of breast cancer patient-derived CD133^high/CXCR4^high/ALDH1^high cancer stem-like cells (CSLCs), which showed very low KRT19 and high Notch1 expression. Taken together, our study suggests a novel function for KRT19 in the regulation of nuclear import of the β-catenin/RAC1 complex, thus modulating the NUMB-dependent Notch Signaling Pathway in breast cancers and CSLCs, which might bear potential clinical implications for cancer or CSLC treatment.
-
krt19 directly interacts with β catenin rac1 complex to regulate numb dependent Notch Signaling Pathway and breast cancer properties
Oncogene, 2017Co-Authors: S K Saha, H Y Choi, A A Dayem, Bongwoo Kim, Gwangmo Yang, Kyeongseok Kim, Yingfu Yin, Ssanggoo ChoAbstract:Studies have reported that interactions between keratins (KRTs) and other proteins initiate Signaling cascades that regulate cell migration, invasion, and metastasis. In the current study, we found that expression of KRT19 was specifically high in breast cancers and significantly correlated with their invasiveness. Moreover, knockdown of KRT19 led to increased proliferation, migration, invasion, drug resistance, and sphere formation in breast cancer cells via an upregulated Notch Signaling Pathway. This was owing to reduced expression of NUMB, an inhibitory protein of the Notch Signaling Pathway. In addition, we found that KRT19 interacts with β-catenin/RAC1 complex and enhances the nuclear translocation of β-catenin. Concordantly, knockdown of KRT19 suppressed the nuclear translocation of β-catenin as well as β-catenin-mediated NUMB expression. Furthermore, modulation of KRT19-mediated regulation of NUMB and Notch1 expression led to the repression of the cancer stem cell properties of breast cancer patient-derived CD133high/CXCR4high/ALDH1high cancer stem-like cells (CSLCs), which showed very low KRT19 and high Notch1 expression. Taken together, our study suggests a novel function for KRT19 in the regulation of nuclear import of the β-catenin/RAC1 complex, thus modulating the NUMB-dependent Notch Signaling Pathway in breast cancers and CSLCs, which might bear potential clinical implications for cancer or CSLC treatment.
