MAPK Pathway The MAPK pathway is one of the well studied pathways which connect different types of membrane receptors when there is mitogenic differentiation or stimulation. This pathway is involved in cell differentiation, proliferation, apoptosis and migration. Regulation of migration is crucial in various instances such as the embryonic cell layer movement during development, wound healing, inflammation etc. While unregulated migration is the hallmark of tumor invasion. Cells will migrate towards the direction of chemical signals like epidermal growth factor, keratin growth factor, insulin like growth factor etc (van Golen et al., 2002).
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It has been shown that platelets, which are transient cells in BM microenvironment, are important for metastasis of a variety of solid tumors (Figure 1). Platelets bind circulating tumor cells, protecting them against anoikis (a type of programmed cell death occurring due to detachment of the cell from surrounding ECM) as well as against the innate immune system (2, 56, 57). Platelet-derived TGF-β and direct contact between platelets and tumor cells synergistically activate TGF-β/Smad and NF-κB pathways, leading to epithelial-mesenchymal transition (EMT), increased invasion and metastasis (58). In addition, during platelet aggregation by breast cancer cells, platelet-derived lysophosphatidic acid (LPA) induces the release of IL-6 and IL-8 from breast cancer cells, which eventually lead to osteoclastic activation and bone resorption (59). Megakaryocyte ploidy is significantly higher in patients with metastatic disease.
Linley AJ, Mathieu MG, Miles AK, Rees RC, McArdle SE, Regad T. (2012). The helicase HAGE expressed by malignant melanoma-initiating cells is required for tumor cell proliferation In Vivo. The journal of biological chemistry. DOI: 10.1074/jbc.M111.308973. 6.
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