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Synthetic Compounds vs. Phytochemicals for the Treatment of Human Cutaneous Malignant Melanoma
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Jacqueline Maphutha, Namrita Lall
Melanocytes are connected to keratinocytes under normal physiological conditions through E-cadherin; the link between melanocytes and keratinocytes necessitates the normal functioning of melanocytes. An epithelial to mesenchymal transition enables the expression of neural cadherin (N-cadherin) instead of E-cadherin. Neural cadherin enables melanomas to migrate from the epidermis into the dermis enabling metastasis. Therefore, N-cadherin leads to the hyperactivation of the PI3K/Akt/mTOR pathway (Liu and Sheikh, 2014; Mrozik et al., 2018).
Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Interestingly, the SNAIL signaling pathway triggers breast cancer metastasis but has no relevance in pancreatic cancer models. Also, EMT can be reversed via Mesenchymal-Epithelial Transition (MET) which is thought to facilitate the implanting of circulating tumor cells to develop secondary tumors when they reach a desirable target metastatic site. As part of this processes, the Extracellular Matrix (ECM) must be degraded, which is carried out by a proteolytic enzyme family, the Matrix Metalloproteinases (MMPs). These enzymes are key to tumor invasion, allowing tumor cells to degrade the ECM, penetrate the basement membrane, and move to other sites. MMPs also regulate cellular adhesion, which makes it easier for tumor cells to migrate. Cell Adhesion Molecules (CAMs) also play a significant role in tumor development and metastases, and include four groups: the Cadherins, Selectins, Integrins, and the Immunoglobulin Superfamily. A reduction or loss in Cadherin expression has been observed in some epithelial cancers, which is associated with increased invasion and metastasis. Activation of CAM proteins, including kinases and chemokines, can induce downstream signaling pathways, which ultimately promotes tumor growth and progression. Some chemopreventive agents are thought to work by inhibiting key regulators to suppress tumor invasion and metastasis.
Cell Components and Function
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
Most cells except for red blood cells have integral membrane proteins that attach to the extracellular matrix or with adhesion molecules on neighbouring cells. These molecules hold the tissue together and permit the transmission of mechanical forces from one cell to another. Some also act as receptors. The integrins are cell-matrix adhesion molecules that link cells to fibronectin or laminin in the extracellular matrix. The cadherins are glycoproteins that mediate Ca-dependent cell–cell adhesion. They bind to a copy of the molecule to cadherins on the other molecule. Intercellular adhesion molecules (ICAMS) are expressed on capillary endothelial cell surfaces that are activated by infection of surrounding tissue. They bind to integrins on white cells and promote their movement to sites of infection. Selectins are carbohydrate binding proteins on endothelial cell membranes that recognize sugars on white blood cell surfaces and form the initial binding, which is strengthened by ICAMs.
Dual role of E-cadherin in cancer cells
Published in Tissue Barriers, 2022
Svetlana N. Rubtsova, Irina Y. Zhitnyak, Natalya A. Gloushankova
Loss of E-cadherin plays an important role in tumor progression. Down-regulation of E-cadherin expression detected in various carcinomas correlates with aggressive behavior of the tumors and is considered a prognostic factor associated with poor patient survival.39 Disruption of E-cadherin-based AJs between tumor cells facilitates their ability to migrate away from the tumor and invade adjacent tissues. Molecular mechanisms of E-cadherin down-regulation in tumors have been studied in great detail (Figure 2). Germline mutations inactivating the E-cadherin gene CDH1 and the subsequent loss of the E-cadherin protein were described in hereditary forms of diffuse gastric cancers and lobular breast cancers.40,41 Loss of heterozygosity on chromosome arm 16q in combination with a mutation of the other allele leading to CDH1 inactivation was revealed in many cases of hepatocellular carcinoma,42,43 prostate adenocarcinoma,44 and infiltrating lobular breast carcinoma.45,46 Aberrant methylation of the CDH1 gene promoter and the associated loss of E-cadherin expression was demonstrated in diffuse type gastric cancer and lobular breast carcinoma.47–49 In some cases, loss of E-cadherin in combination with inactivation of p53 or Pten has a causal role in tumor development as has been shown, for example, for invasive lobular breast carcinoma and diffuse type gastric cancer.50–52
Altered expression of junctional proteins as a potential biomarker in oral precancerous and cancerous patients
Published in Tissue Barriers, 2022
Puja Upadhaya, Sarbani Giri, Dharmeswar Barhoi, Abhinandan Bhattacharjee
Cadherins are major components of AJs and serve a key role in the maintenance of epithelial tissue integrity.13 E-cadherin (E-cad) is a 120 KD transmembrane glycoprotein belonging to AJs and a major calcium-dependent cell surface adhesion molecule.14 It is encoded by the CDH1 gene located on chromosome 16q-224 and is restricted to the surface of the epithelial cells.15 It is a widely distributed, intercellular adhesion molecule16 that through its cytoplasmic tail, associates with various intracellular proteins.17 It functions in cellular crosstalk and mediates cell-to-cell communication by protein interactions on the cytoplasmic membrane surfaces. Reports suggest the role of E-cad as a biomarker in detecting gene expression and predicting disease progression.18 Therefore, investigation of E-cad might be a promising area of interest and could be a potential biological marker.
The mechanisms of resistance to second- and third-generation ALK inhibitors and strategies to overcome such resistance
Published in Expert Review of Anticancer Therapy, 2021
Naoki Haratake, Gouji Toyokawa, Takashi Seto, Tetsuzo Tagawa, Tasuro Okamoto, Koji Yamazaki, Sadanori Takeo, Masaki Mori
The epithelial-to-mesenchymal transition (EMT) is another histological transformation found in some cases that are resistant to several anticancer treatments, including EGFR- and ALK-TKIs, which manifests as a series of cellular alterations favoring a more invasive, mesenchymal phenotype [65,66]. The EMT is the process through which cells downregulate their epithelial characteristics and acquire a mesenchymal phenotype. The EMT cause fibrosis, tumor invasion, and cancer progression [65]. Under the EMT, the junction of epithelial cells is lost, their cytoskeletons are reorganized, and their gene expression is reprogrammed to acquire motility and an invasive phenotype. E-cadherin is an epithelial marker that maintains cell–cell adhesion and inhibits cell mobility and invasiveness. Vimentin is a type III intermediate filament that is a marker of the mesenchymal phenotype of the EMT. The downregulation of the expression of E-cadherin and the concomitant upregulation of the expression of vimentin are common indicators of the EMT in carcinomas [66].