Principles of oncology
Professor Sir Norman Williams, Professor P. Ronan O’Connell, Professor Andrew W. McCaskie in Bailey & Love's Short Practice of Surgery, 2018
membrane and gain direct access to blood and lymph vessels. Cancer cells use three main mechanisms to facilitate invasion: (1) they cause a rise in the interstitial pressure within a tissue; (2) they secrete enzymes that dissolve extracellular matrix; and (3) they become mobile. Unrestrained proliferation and a lack of contact inhibition enable cancer cells to exert pressure directly on the surrounding tissue and push beyond the normal limits. They secrete collagenases and proteases that chemically dissolve any extracellular boundaries that would otherwise limit their spread through tissues and, by modulating the expression of cell-surface molecules called integrins, are able to detach themselves from the extracellular matrix. The abnormal integrins associated with malignancy can also transmit signals from the environment to the cytoplasm and nucleus of the cancer cells (‘outside-in signalling’) and these signals can induce increased motility. These processes are similar to those involved in normal development, in the migration of the neural crest or the formation of the heart. Epithelial cells behave as if they were mesenchymal cells and the process is termed ‘epithelial– mesenchymal transition’ (EMT). EMT is a crucial step in malignant transformation and many of the genes and proteins implicated in the formation of cancer control processes are involved in EMT, for example Src, Ras, integrins, Wnt /b –catenin, Notch.
New knowledge about adenomyosis
Carlos Simón, Linda C. Giudice in The Endometrial Factor, 2017
The presence of endometrial stromal cells in the myometrial compartment could also derive from perivascular cells through mechanisms involved in stromal to smooth muscle differentiation, but this does not explain the derivation of the epithelial component. One possibility is that the epithelium develops through direct extension from the basalis or from adjacent foci. Alternatively, this may arise through mechanisms involving epithelial–mesenchymal transition (EMT) (61). This phenomenon is believed to be estrogen dependent and may be important to the acquisition of invasive properties by epithelial cells. In women with adenomyosis, Chen et al. (62,63) found increased vimentin and reduced E-cadherin in ectopic, but not in eutopic, endometrium, providing evidence for EMT, and that serum estradiol negatively correlated with E-cadherin expression in the epithelium of the eutopic endometrium and in adenomyotic lesions, suggesting a role of estradiol in the process. Furthermore, they observed that Ishikawa endometrial epithelial cells undergo morphological changes acquiring a fibroblast-like phenotype in response to estrogen, and that these cells also exhibit a shift from epithelial-to-mesenchymal marker expression, increased migration and invasion, and upregulation of the EMT regulator Slug.
Chemopreventive Agents
David E. Thurston, Ilona Pysz in Chemistry and Pharmacology of Anticancer Drugs, 2021
Metastasis is a complex process involving the spread of tumor cells from the primary tumor to distant sites where secondary and tertiary tumors can form (Figure 12.4). The Epithelial-Mesenchymal Transition (EMT) is an essential event in the initial phase of metastasis, a process which also occurs during normal embryonic development, tissue regeneration, and wound healing. However, the EMT process is often not completed in tumor cells which are frequently in multiple transitional states and expressing mixed epithelial and mesenchymal genes. These hybrid cells can move collectively as clusters and behave more aggressively than normal cells, with the transition in gene expression often triggered by complex signaling pathways such as those controlled by the transcription factors SNAI1/2, ZEB1/2, and Twist. However, the role of these transcription factors in EMT is complex, and their functions are not tissue specific.
GDF15 promotes epithelial-to-mesenchymal transition in colorectal
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Yifei Zhang, Xixun Wang, Menglai Zhang, Zhenbin Zhang, Lixin Jiang, Leping Li
The epithelial to mesenchymal transition (EMT) is a process characterized by loss of cell–cell adhesion and gain of migratory and invasive traits. The transdifferentiation from quiescent epithelial cells into motile mesenchymal cells is essential for embryogenesis, fibrosis, tissue repair, wound healing and tumour progression [9,10]. Under pathological conditions, the EMT occurs at the initial stage of cancer metastasis. A number of key transcription factors were identified to potentiate EMT progression such as TWIST, ZEB1, ZEB2, SNAIL1 and SNAIL2 [11,12]. Meanwhile, the expression of mesenchymal markers vimentin would increase and hence contribute to cell motility and adhesion [13]. This is one of the most important mechanisms that promotes metastasis and thereby increases tumour aggressiveness. GDF15 is one of the most important transcriptional regulators, which promotes the EMT process and metastasis in malignancy by inducing the expression of certain EMT regulators, such as Snail, ZEB1, TWIST and so on [14–16]. However, whether GDF15 activates other critical EMT regulators in CRC, which may have differential and non-redundant roles, remains to be explored further.
EHD2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Human Colon Cancer
Published in Cancer Investigation, 2021
Chengqi Guan, Cuihua Lu, Mingbing Xiao, Weichang Chen
In order to investigate the role of EHD2 in colon cancer pathogenesis, EHD2 expression was detected in four colon cancer cells, and SW620 cells had the lowest EHD2 mRNA (Figure 3(A)) and protein (Figure 3(B)) expression. After lentiviral‐mediated transfection targeting EHD2 in SW620 cells, transfected cells showed significantly increased EHD2 protein levels compared with the control. Results of the western blot analysis showed that EHD2 overexpression markedly increased the expression of epithelial marker E-cadherin, but decreased the expression of mesenchymal marker N-cadherin and the transcription factor mediating epithelial-mesenchymal transition (EMT), Snail in cells (Figure 3(C,D)). To further verify the function of EHD2 in colon cancer on cell migration and invasion, LV-EHD2 was subjected to wound-healing assay (Figure 3(E,F)) and Transwell assay (Figure 3(G,H)). EHD2 overexpression was found to inhibit cell migration. Taken together, EHD2 depressed colon carcinoma cell EMT, invasion, and migration.
High Expression of TRIM15 Is Associated with Tumor Invasion and Predicts Poor Prognosis in Patients with Gastric Cancer
Published in Journal of Investigative Surgery, 2021
Weiran Zhou, Hao Chen, Yuanyuan Ruan, Xiaoqing Zeng, Fenglin Liu
As we know, epithelial-mesenchymal transition is an essential progress in tumor invasion and metastasis. Here we up-regulate TRIM15 expression in MGC80-3 and HGC-27 cells (Figure 4A-B) and found that compared with the control, epithelial markers E-cadherin was down-regulated while the mesenchymal marker N-cadherin and Vimentin as well as the transcriptional repressors Snail were up-regulated in TRIM15-overexpressing cells (Figure 4C). To gain more insight, cell migration and invasion was compared between normal and TRIM15-overpressed cells (Figure 4D–H). Transwell assays demonstrated that gastric cancer cells exhibited a higher migratory and invasive potential when TRIM15 expression was increased (Figure 4F–G). We also performed the wound healing assay and found that MGC80-3 and HGC-27 cells transfected with TRIM15 overexpression plasmids had enhanced migratory potential (Figure 4H). These data suggested the role of up-regulated TRIM15 expression in cellular processes for metastasis.