scholarly journals Molecular Events in Primary and Metastatic Colorectal Carcinoma: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Rani Kanthan ◽  
Jenna-Lynn Senger ◽  
Selliah Chandra Kanthan
Keyword(s):  
Colorectal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Cpg Island ◽  
Genetic Alterations ◽  
Tumour Suppressor Genes ◽  
Metastatic Colorectal Carcinoma ◽  
Cpg Island Methylator Phenotype ◽  
Mesenchymal Transition ◽  
Sequence Of Events ◽  
Molecular Events

Colorectal cancer (CRC) is a heterogeneous disease, developing through a multipathway sequence of events guided by clonal selections. Pathways included in the development of CRC may be broadly categorized into (a) genomic instability, including chromosomal instability (CIN), microsatellite instability (MSI), and CpG island methylator phenotype (CIMP), (b) genomic mutations including suppression of tumour suppressor genes and activation of tumour oncogenes, (c) microRNA, and (d) epigenetic changes. As cancer becomes more advanced, invasion and metastases are facilitated through the epithelial-mesenchymal transition (EMT), with additional genetic alterations. Despite ongoing identification of genetic and epigenetic markers and the understanding of alternative pathways involved in the development and progression of this disease, CRC remains the second highest cause of malignancy-related mortality in Canada. The molecular events that underlie the tumorigenesis of primary and metastatic colorectal carcinoma are detailed in this manuscript.

scholarly journals Vimentin Is at the Heart of Epithelial Mesenchymal Transition (EMT) Mediated Metastasis

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4985
Author(s):  
Saima Usman ◽  
Naushin H. Waseem ◽  
Thuan Khanh Ngoc Nguyen ◽  
Sahar Mohsin ◽  
Ahmad Jamal ◽  
...  
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Cells ◽  
Type I ◽  
Mortality And Morbidity ◽  
Mesenchymal Transition ◽  
Type Iii ◽  
Tumour Spread ◽  
Molecular Events

Epithelial-mesenchymal transition (EMT) is a reversible plethora of molecular events where epithelial cells gain the phenotype of mesenchymal cells to invade the surrounding tissues. EMT is a physiological event during embryogenesis (type I) but also happens during fibrosis (type II) and cancer metastasis (type III). It is a multifaceted phenomenon governed by the activation of genes associated with cell migration, extracellular matrix degradation, DNA repair, and angiogenesis. The cancer cells employ EMT to acquire the ability to migrate, resist therapeutic agents and escape immunity. One of the key biomarkers of EMT is vimentin, a type III intermediate filament that is normally expressed in mesenchymal cells but is upregulated during cancer metastasis. This review highlights the pivotal role of vimentin in the key events during EMT and explains its role as a downstream as well as an upstream regulator in this highly complex process. This review also highlights the areas that require further research in exploring the role of vimentin in EMT. As a cytoskeletal protein, vimentin filaments support mechanical integrity of the migratory machinery, generation of directional force, focal adhesion modulation and extracellular attachment. As a viscoelastic scaffold, it gives stress-bearing ability and flexible support to the cell and its organelles. However, during EMT it modulates genes for EMT inducers such as Snail, Slug, Twist and ZEB1/2, as well as the key epigenetic factors. In addition, it suppresses cellular differentiation and upregulates their pluripotent potential by inducing genes associated with self-renewability, thus increasing the stemness of cancer stem cells, facilitating the tumour spread and making them more resistant to treatments. Several missense and frameshift mutations reported in vimentin in human cancers may also contribute towards the metastatic spread. Therefore, we propose that vimentin should be a therapeutic target using molecular technologies that will curb cancer growth and spread with reduced mortality and morbidity.

scholarly journals Autocrine hGH stimulates oncogenicity, epithelial-mesenchymal transition and cancer stem cell-like behavior in human colorectal carcinoma

Oncotarget ◽  
2017 ◽  
Vol 8 (61) ◽  
pp. 103900-103918 ◽  
Author(s):  
Jing-Jing Wang ◽  
Qing-Yun Chong ◽  
Xin-Bao Sun ◽  
Ming-Liang You ◽  
Vijay Pandey ◽  
...  
Keyword(s):  
Stem Cell ◽  
Colorectal Carcinoma ◽  
Cancer Stem Cell ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Human Colorectal Carcinoma

Smad4 and epithelial–mesenchymal transition proteins in colorectal carcinoma: an immunohistochemical study

2018 ◽  
Vol 49 (3) ◽  
pp. 235-244 ◽  
Author(s):  
M. Ioannou ◽  
E. Kouvaras ◽  
R. Papamichali ◽  
M. Samara ◽  
I. Chiotoglou ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Study ◽  
Mesenchymal Transition

scholarly journals ARID1A, a SWI/SNF subunit, is critical to acinar cell homeostasis and regeneration and is a barrier to transformation and epithelial-mesenchymal transition in the pancreas

Gut ◽  
2018 ◽  
Vol 68 (7) ◽  
pp. 1245-1258 ◽  
Author(s):  
Wenjia Wang ◽  
Scott C Friedland ◽  
Bing Guo ◽  
Michael R O’Dell ◽  
William B Alexander ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Lines ◽  
Genetic Alterations ◽  
Homozygous Deletion ◽  
Ductal Adenocarcinoma ◽  
Interaction Domain ◽  
Mesenchymal Transition ◽  
Poorly Differentiated

ObjectiveHere, we evaluate the contribution of AT-rich interaction domain-containing protein 1A (ARID1A), the most frequently mutated member of the SWItch/sucrose non-fermentable (SWI/SNF) complex, in pancreatic homeostasis and pancreatic ductal adenocarcinoma (PDAC) pathogenesis using mouse models.DesignMice with a targeted deletion of Arid1a in the pancreas by itself and in the context of two common genetic alterations in PDAC, Kras and p53, were followed longitudinally. Pancreases were examined and analysed for proliferation, response to injury and tumourigenesis. Cancer cell lines derived from these models were analysed for clonogenic, migratory, invasive and transcriptomic changes.ResultsArid1a deletion in the pancreas results in progressive acinar-to-ductal metaplasia (ADM), loss of acinar mass, diminished acinar regeneration in response to injury and ductal cell expansion. Mutant Kras cooperates with homozygous deletion of Arid1a, leading to intraductal papillary mucinous neoplasm (IPMN). Arid1a loss in the context of mutant Kras and p53 leads to shorter tumour latency, with the resulting tumours being poorly differentiated. Cancer cell lines derived from Arid1a-mutant tumours are more mesenchymal, migratory, invasive and capable of anchorage-independent growth; gene expression analysis showed activation of epithelial-mesenchymal transition (EMT) and stem cell identity pathways that are partially dependent on Arid1a loss for dysregulation.ConclusionsARID1A plays a key role in pancreatic acinar homeostasis and response to injury. Furthermore, ARID1A restrains oncogenic KRAS-driven formation of premalignant proliferative IPMN. Arid1a-deficient PDACs are poorly differentiated and have mesenchymal features conferring migratory/invasive and stem-like properties.

scholarly journals The activating transcription factor 2: an influencer of cancer progression

Mutagenesis ◽  
2019 ◽  
Vol 34 (5-6) ◽  
pp. 375-389 ◽  
Author(s):  
Kerstin Huebner ◽  
Jan Procházka ◽  
Ana C Monteiro ◽  
Vijayalakshmi Mahadevan ◽  
Regine Schneider-Stock
Keyword(s):  
Pancreatic Cancer ◽  
Transcription Factor ◽  
3D Structure ◽  
Genetic Alterations ◽  
Tumour Suppressor Genes ◽  
Subcellular Localisation ◽  
Dependent Manner ◽  
Continuous Increase ◽  
Mesenchymal Transition ◽  
Activating Transcription Factor

Abstract In contrast to the continuous increase in survival rates for many cancer entities, colorectal cancer (CRC) and pancreatic cancer are predicted to be ranked among the top 3 cancer-related deaths in the European Union by 2025. Especially, fighting metastasis still constitutes an obstacle to be overcome in CRC and pancreatic cancer. As described by Fearon and Vogelstein, the development of CRC is based on sequential mutations leading to the activation of proto-oncogenes and the inactivation of tumour suppressor genes. In pancreatic cancer, genetic alterations also attribute to tumour development and progression. Recent findings have identified new potentially important transcription factors in CRC, among those the activating transcription factor 2 (ATF2). ATF2 is a basic leucine zipper protein and is involved in physiological and developmental processes, as well as in tumorigenesis. The mutation burden of ATF2 in CRC and pancreatic cancer is rather negligible; however, previous studies in other tumours indicated that ATF2 expression level and subcellular localisation impact tumour progression and patient prognosis. In a tissue- and stimulus-dependent manner, ATF2 is activated by upstream kinases, dimerises and induces target gene expression. Dependent on its dimerisation partner, ATF2 homodimers or heterodimers bind to cAMP-response elements or activator protein 1 consensus motifs. Pioneering work has been performed in melanoma in which the dual role of ATF2 is best understood. Even though there is increasing interest in ATF2 recently, only little is known about its involvement in CRC and pancreatic cancer. In this review, we summarise the current understanding of the underestimated ‘cancer gene chameleon’ ATF2 in apoptosis, epithelial-to-mesenchymal transition and microRNA regulation and highlight its functions in CRC and pancreatic cancer. We further provide a novel ATF2 3D structure with key phosphorylation sites and an updated overview of all so-far available mouse models to study ATF2 in vivo.

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