The Experts below are selected from a list of 84 Experts worldwide ranked by ideXlab platform
Gopesh Srivastava - One of the best experts on this subject based on the ideXlab platform.
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oncogenic properties of a novel gene jk 1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2007Co-Authors: Wing K Tang, C H Chui, Tian M Ou, Mei M Wong, Sarwat Fatima, Gopesh Srivastava, John Wong, S W Tsao, Albert S C Chan, Kwok Ping HoAbstract:Esophageal squamous cell carcinoma (ESCC) shows high frequency and mortality in Asian regions, including China. Previous analysis of genomic DNA of ESCC using comparative genomic hybridization indicated that amplification of the chromosome 5p regions is a common event in ESCC cell lines and patient cases of Hong Kong Chinese origin, and the results suggested that the genes located in the chromosome 5p regions may play crucial roles in the molecular pathogenesis of ESCC. Our previous studies on ESCC confirmed the tumorigenic and overexpression properties of a novel gene JS-1 located in chromosome 5p15.2 upstream to Delta-Catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to Delta-Catenin was characterized for its roles in the pathogenesis of ESCC. Thirteen ESCC cell lines and 30 surgical specimens of esophageal tumors were studied for the overexpression of JK-1 using multiplex RT-PCR analysis. The transforming capacity of overexpression of JK-1 was also investigated by transfecting NIH 3T3 and HEK 293 cells with the expression vector cloned with JK-1, followed by the soft agar and foci formation assays. JK-1 was overexpressed in 9/13 (69%) of the ESCC cell lines and 9/30 (30%) of the ESCC patient cases. Both NIH 3T3 and HEK 293 cells acquired the properties of anchorage-dependent and -independent growth when JK-1 was overexpressed. Most significantly, subcutaneous sarcomas were formed in all (3/3) the athymic nude mice after NIH 3T3 cells overexpressing JK-1 were injected subcutaneously. Our results thus indicated that JK-1 is commonly overexpressed in ESCC and has a prominent capacity to transform normal cells. Our overall results thus provide the first evidence that the overexpression of JK-1 and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC.
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transforming capacity of two novel genes js 1 and js 2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2006Co-Authors: Sarwat Fatima, Wing K Tang, C H Chui, Mei M Wong, John Wong, S W Tsao, Ho W Au, Wing Y Li, Filly Cheung, Gopesh SrivastavaAbstract:: Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to Delta Catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC. The present study also forms the ground work for further identification of novel mechanisms of molecular carcinogenesis in ESCC and other cancers.
Kenneth S. Kosik - One of the best experts on this subject based on the ideXlab platform.
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deletion of the neuron specific protein Delta Catenin leads to severe cognitive and synaptic dysfunction
Current Biology, 2004Co-Authors: Inbal Israely, Kenneth S. Kosik, Rui M Costa, C W Xie, Alcino J Silva, Xin LiuAbstract:Abstract Delta-Catenin (δ-Catenin) is a neuron-specific Catenin, which has been implicated in adhesion and dendritic branching [1, 2]. Moreover, deletions of δ-Catenin correlate with the severity of mental retardation in Cri-du-Chat syndrome (CDCS), which may account for 1% of all mentally retarded individuals [3]. Interestingly, δ-Catenin was first identified through its interaction with Presenilin-1 (PS1), the molecule most frequently mutated in familial Alzheimer's Disease (FAD) [4]. We investigated whether deletion of δ-Catenin would be sufficient to cause cognitive dysfunction by generating mice with a targeted mutation of the δ-Catenin gene ( δ-cat −/− ). We observed that δ-cat −/− animals are viable and have severe impairments in cognitive function. Furthermore, mutant mice display a range of abnormalities in hippocampal short-term and long-term synaptic plasticity. Also, N-cadherin and PSD-95, two proteins that interact with δ-Catenin [1, 5], are significantly reduced in mutant mice. These deficits are severe but specific because δ-cat −/− mice display a variety of normal behaviors, exhibit normal baseline synaptic transmission, and have normal levels of the synaptic adherens proteins E-cadherin and β-Catenin. These data reveal a critical role for δ-Catenin in brain function and may have important implications for understanding mental retardation syndromes such as Cri-du-Chat and neurodegenerative disorders, such as Alzheimer's disease, that are characterized by cognitive decline.
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brain armadillo protein δ Catenin interacts with abl tyrosine kinase and modulates cellular morphogenesis in response to growth factors
Journal of Neuroscience Research, 2002Co-Authors: N K Mukhopadhyay, Miguel Medina, J D Griffin, Mercedes F Paredes, Kenneth S. KosikAbstract:Delta-Catenin associates with adhesive junctions and facilitates cellular morphogenesis (Lu et al., 1999). Here we show that Delta-Catenin colocalizes with actin filaments and Abl tyrosine kinase in the growth cones of cultured hippocampal neurons. PC12 cells induced to express Delta-Catenin show accelerated neurite extension upon nerve growth factor (NGF) stimulation. STI571, an Abl family kinase inhibitor, further accentuates these stimulatory effects. Delta-Catenin is a potent substrate for Abl in vitro using an immunocomplex assay and most of the Abl-induced tyrosine phosphorylation within cells is present in the N-terminus of Delta-Catenin. When Delta-Catenin-expressing epithelial cells are induced to scatter in response to hepatocyte growth factor (HGF), STI571 leads to the rapid redistribution of Delta-Catenin and changes in cellular morphology. We suggest that Delta-Catenin is a possible Abl substrate and acts downstream of Abl to orchestrate actin-based cellular morphogenesis.
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Delta Catenin is a nervous system specific adherens junction protein which undergoes dynamic relocalization during development
The Journal of Comparative Neurology, 2000Co-Authors: Jianhua Zhou, Miguel Medina, Tomohide Goto, Margaretha Jacobson, Pradeep G Bhide, Kenneth S. KosikAbstract:Delta-Catenin is a member of the Armadillo repeat family and component of the adherens junction discovered in a two-hybrid assay as a bona fide interactor with presenilin-1 (Zhou et al., [1997], NeuroReport 8:2085-2090), a protein which carries mutations that cause familial Alzheimer's disease. The expression pattern of Delta-Catenin was mapped between embryonic day 10 (E10) and adulthood by Northern blots, in situ hybridization and immunohistochemistry in the mouse. In development, Delta-Catenin is dynamically regulated with respect to its site of expression. It is first expressed within proliferating neuronal progenitor cells of the neuroepithelium, becomes down-regulated during neuronal migration, and is later reexpressed in the dendritic compartment of postmitotic neurons. In the mouse, Delta-Catenin mRNA is expressed by E10, increases and peaks at postnatal day (P)7, with lower levels in adulthood. In the developing neocortex, Delta-Catenin mRNA is strongly expressed in the proliferative ventricular zone and the developing cortical plate, yet is conspicuously less prominent in the intermediate zone, which contains migrating cortical neurons, Delta-Catenin protein forms a honeycomb pattern in the neuroepithelium by labeling the cell periphery in a typical adherens junction pattern. By E18, Delta-Catenin expression shifts primarily to nascent apical dendrites, a pattern that continues through adulthood. The dynamic relocalization of Delta-Catenin expression during development, taken together with previously published data which described a role for Delta-Catenin in cell motility (Lu et al., [1999] J. Cell. Biol. 144:519-532), suggests the hypothesis that Delta-Catenin regulation is closely linked to neuronal migration and may play a role in the establishment of mature dendritic relationships in the neuropil.
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presenilin 1 interaction in the brain with a novel member of the armadillo family
Neuroreport, 1997Co-Authors: Jianhua Zhou, Miguel Medina, Udaya Liyanage, Andrew Simmons, Michael Lovett, Kenneth S. KosikAbstract:One approach to understanding the function of presenilin 1 (PS1), is to discover those proteins with which it interacts. Evidence for a function in developmental patterning came from C. elegans, in which a PS homologue was identified by screening for suppressors of a mutation in Notch/lin-12, a gene which specifies cell fate. However, this genetic experiment cannot determine which proteins directly interact with PS1. Therefore, we utilized the two hybrid system and confirmatory co-immunoprecipitations to identify a novel Catenin, termed Delta-Catenin, which interacts with PS1 and is principally expressed in brain. The Catenins are a gene family related to the Armadillo gene in Drosophila, some of which appear to have dual roles-they are components of cell-cell adherens junctions, and may serve as intermediates in the Wingless (Wg) signaling pathway, which, like Notch/lin-12, is also responsible for a variety of inductive signaling events. In the non-neuronal 293 cell line, PS1 interacted with beta-Catenin, the family member with the greatest homology to Armadillo. Wg and Notch interactions are mediated by the Dishevelled gene, which may form a signaling complex with PS1 and Wg pathway intermediates to regulate the function of the Notch/lin-12 gene.
Sarwat Fatima - One of the best experts on this subject based on the ideXlab platform.
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oncogenic properties of a novel gene jk 1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2007Co-Authors: Wing K Tang, C H Chui, Tian M Ou, Mei M Wong, Sarwat Fatima, Gopesh Srivastava, John Wong, S W Tsao, Albert S C Chan, Kwok Ping HoAbstract:Esophageal squamous cell carcinoma (ESCC) shows high frequency and mortality in Asian regions, including China. Previous analysis of genomic DNA of ESCC using comparative genomic hybridization indicated that amplification of the chromosome 5p regions is a common event in ESCC cell lines and patient cases of Hong Kong Chinese origin, and the results suggested that the genes located in the chromosome 5p regions may play crucial roles in the molecular pathogenesis of ESCC. Our previous studies on ESCC confirmed the tumorigenic and overexpression properties of a novel gene JS-1 located in chromosome 5p15.2 upstream to Delta-Catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to Delta-Catenin was characterized for its roles in the pathogenesis of ESCC. Thirteen ESCC cell lines and 30 surgical specimens of esophageal tumors were studied for the overexpression of JK-1 using multiplex RT-PCR analysis. The transforming capacity of overexpression of JK-1 was also investigated by transfecting NIH 3T3 and HEK 293 cells with the expression vector cloned with JK-1, followed by the soft agar and foci formation assays. JK-1 was overexpressed in 9/13 (69%) of the ESCC cell lines and 9/30 (30%) of the ESCC patient cases. Both NIH 3T3 and HEK 293 cells acquired the properties of anchorage-dependent and -independent growth when JK-1 was overexpressed. Most significantly, subcutaneous sarcomas were formed in all (3/3) the athymic nude mice after NIH 3T3 cells overexpressing JK-1 were injected subcutaneously. Our results thus indicated that JK-1 is commonly overexpressed in ESCC and has a prominent capacity to transform normal cells. Our overall results thus provide the first evidence that the overexpression of JK-1 and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC.
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transforming capacity of two novel genes js 1 and js 2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2006Co-Authors: Sarwat Fatima, Wing K Tang, C H Chui, Mei M Wong, John Wong, S W Tsao, Ho W Au, Wing Y Li, Filly Cheung, Gopesh SrivastavaAbstract:: Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to Delta Catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC. The present study also forms the ground work for further identification of novel mechanisms of molecular carcinogenesis in ESCC and other cancers.
Wing K Tang - One of the best experts on this subject based on the ideXlab platform.
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oncogenic properties of a novel gene jk 1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2007Co-Authors: Wing K Tang, C H Chui, Tian M Ou, Mei M Wong, Sarwat Fatima, Gopesh Srivastava, John Wong, S W Tsao, Albert S C Chan, Kwok Ping HoAbstract:Esophageal squamous cell carcinoma (ESCC) shows high frequency and mortality in Asian regions, including China. Previous analysis of genomic DNA of ESCC using comparative genomic hybridization indicated that amplification of the chromosome 5p regions is a common event in ESCC cell lines and patient cases of Hong Kong Chinese origin, and the results suggested that the genes located in the chromosome 5p regions may play crucial roles in the molecular pathogenesis of ESCC. Our previous studies on ESCC confirmed the tumorigenic and overexpression properties of a novel gene JS-1 located in chromosome 5p15.2 upstream to Delta-Catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to Delta-Catenin was characterized for its roles in the pathogenesis of ESCC. Thirteen ESCC cell lines and 30 surgical specimens of esophageal tumors were studied for the overexpression of JK-1 using multiplex RT-PCR analysis. The transforming capacity of overexpression of JK-1 was also investigated by transfecting NIH 3T3 and HEK 293 cells with the expression vector cloned with JK-1, followed by the soft agar and foci formation assays. JK-1 was overexpressed in 9/13 (69%) of the ESCC cell lines and 9/30 (30%) of the ESCC patient cases. Both NIH 3T3 and HEK 293 cells acquired the properties of anchorage-dependent and -independent growth when JK-1 was overexpressed. Most significantly, subcutaneous sarcomas were formed in all (3/3) the athymic nude mice after NIH 3T3 cells overexpressing JK-1 were injected subcutaneously. Our results thus indicated that JK-1 is commonly overexpressed in ESCC and has a prominent capacity to transform normal cells. Our overall results thus provide the first evidence that the overexpression of JK-1 and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC.
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transforming capacity of two novel genes js 1 and js 2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2006Co-Authors: Sarwat Fatima, Wing K Tang, C H Chui, Mei M Wong, John Wong, S W Tsao, Ho W Au, Wing Y Li, Filly Cheung, Gopesh SrivastavaAbstract:: Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to Delta Catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC. The present study also forms the ground work for further identification of novel mechanisms of molecular carcinogenesis in ESCC and other cancers.
S W Tsao - One of the best experts on this subject based on the ideXlab platform.
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oncogenic properties of a novel gene jk 1 located in chromosome 5p and its overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2007Co-Authors: Wing K Tang, C H Chui, Tian M Ou, Mei M Wong, Sarwat Fatima, Gopesh Srivastava, John Wong, S W Tsao, Albert S C Chan, Kwok Ping HoAbstract:Esophageal squamous cell carcinoma (ESCC) shows high frequency and mortality in Asian regions, including China. Previous analysis of genomic DNA of ESCC using comparative genomic hybridization indicated that amplification of the chromosome 5p regions is a common event in ESCC cell lines and patient cases of Hong Kong Chinese origin, and the results suggested that the genes located in the chromosome 5p regions may play crucial roles in the molecular pathogenesis of ESCC. Our previous studies on ESCC confirmed the tumorigenic and overexpression properties of a novel gene JS-1 located in chromosome 5p15.2 upstream to Delta-Catenin. In the present study, another novel gene JK-1 which is located at 5p15.1 downstream to Delta-Catenin was characterized for its roles in the pathogenesis of ESCC. Thirteen ESCC cell lines and 30 surgical specimens of esophageal tumors were studied for the overexpression of JK-1 using multiplex RT-PCR analysis. The transforming capacity of overexpression of JK-1 was also investigated by transfecting NIH 3T3 and HEK 293 cells with the expression vector cloned with JK-1, followed by the soft agar and foci formation assays. JK-1 was overexpressed in 9/13 (69%) of the ESCC cell lines and 9/30 (30%) of the ESCC patient cases. Both NIH 3T3 and HEK 293 cells acquired the properties of anchorage-dependent and -independent growth when JK-1 was overexpressed. Most significantly, subcutaneous sarcomas were formed in all (3/3) the athymic nude mice after NIH 3T3 cells overexpressing JK-1 were injected subcutaneously. Our results thus indicated that JK-1 is commonly overexpressed in ESCC and has a prominent capacity to transform normal cells. Our overall results thus provide the first evidence that the overexpression of JK-1 and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC.
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transforming capacity of two novel genes js 1 and js 2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma
International Journal of Molecular Medicine, 2006Co-Authors: Sarwat Fatima, Wing K Tang, C H Chui, Mei M Wong, John Wong, S W Tsao, Ho W Au, Wing Y Li, Filly Cheung, Gopesh SrivastavaAbstract:: Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to Delta Catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC. The present study also forms the ground work for further identification of novel mechanisms of molecular carcinogenesis in ESCC and other cancers.