**2. Formation of metastatic cell**

#### **2.1 Invasion by perturbing cell: Cell and cell matrix adhesion**

Invasion initiates as a result of tumor cell breaking of the basement membrane and penetrate underlying stroma. Tissues architecture forms from epithelium, basement membrane, and stroma. Catherins adhere cells to each other through catenins inside the cell. Integrin receptors attach cells to fibronectin at the extracellular matrix and

fibronectin attaches to collagen. Normally epithelial cells are maintained by cell–cell anchoring junctions: tight junctions- adherent junctions attached to actin and keratin, respectively, whereas cell matrix anchoring junctions hemidesmosomes attached to keratin intermediate filaments like cell-anchoring factor desmosomes. Changes in cell–cell and cell-matrix adhesion are necessary for invasion; these changes must be coordinated with matrix breakdown and cellular mobility. All these molecules provide cell integrity, and therefore, cell adhesion proteins are the target of oncogenes as well as the tumor suppressor proteins that regulate the signaling pathways.

Cadherin functions as tumor suppressor and suppresses tumor cell metastasis at distant sites. Integrins pin cells to basement membrane—extracellular membrane, and cells break free from the binding site during metastasis. Integrins affect the cytoskeleton by binding to actin and key kinases like FAK (Focal Adhesion Kinase). Actually, FAK mediates cell motility and activates the RAS pathway. Therefore, enhancing integrin expression in tumor cells induces mobility and invasion of metastasizing cells. Degradation of extracellular matrix and stroma for invasion of tumor cells to the nearby tissue also depends on proteases [1, 3].

Epithelial-mesenchymal transition involves changes in shape and confers metastatic properties and this process is accompanied by enhancing mobility, invasion, and resistance to apoptotic stimuli. The change provides cells to migrate to distant sites. Epithelial-mesenchymal transition associates with loss of E-cadherin from the adherens junctions and a switch from the expression of keratins to the mesenchymal intermediate-filament vimentin [5].
