Epithelial to mesenchymal transition (EMT) is an important process in embryonic development, tissue repair, inflammation, and cancer. During EMT, epithelial cells disassemble cell-cell adhesions, lose apicobasal polarity, and initiate migratory and invasive processes that allow individual cells to colonize distant sites. It is the means by which non-invasive tumors progress into malignant, metastatic carcinomas. In vitro, EMT occurs in two steps. First, cells spread out, increasing in surface area and pushing the colony borders out. Then cells contract, pulling away from neighboring cells and rupturing cell-cell junctions, resulting in individual highly migratory cells. Recent discoveries indicate that calcium signaling is central in EMT. Both previous data with patch clamping and new calcium imaging data show a series of calcium influxes in cells induced to undergo EMT with hepatocyte growth factor (HGF). It has also been shown that blocking calcium signaling prevents EMT from progressing normally. However, it is not known if calcium alone is sufficient to drive EMT behaviors. By experimentally triggering calcium influxes with an optigenetic cation channel, the behaviors that calcium influxes induce can be determined noninvasively, without use of drugs that may have secondary effects. The results of using the optigenetic set up along with live cell imaging are that cells become more motile and disrupt normal epithelial cell-cell adhesions. This behavior is believed to be due to increased cell contractility downstream of calcium signaling, and is dependent on Ca2+/calmodulin-dependent protein kinase II (CaMKII). When cells are pre-treated with CaMKII inhibitor before HGF addition, they undergo the spreading step of EMT without subsequent cellular contraction and rupture of cell-cell junctions. CaMKII is a protein kinase that is activated by binding Ca2+/calmodulin, and is a known downstream component of calcium signaling. CaMKII is known to affect the actin cytoskeleton by both physically bundling actin filaments to increase their rigidity, and through signaling by activation of myosin light chain kinase (MLCK), which has a role in stress fiber formation. Immunofluorescence did not show colocalization of CaMKII with actin, ruling out regulation through actin bundling. However, CaMKII does appear to have a role in stress fiber formation. EMT induced with HGF treatment results in increased numbers of stress fibers as well as trans-cellular actin network formation, both actin structures decorated with non-muscle myosin II (NMII). CaMKII inhibition not only blocks these actin formations, but it also decreases stress fiber levels below basal unstimulated levels in cells that have not been treated with HGF. This suggests that CaMKII has a role in regulating contractility through cellular actin networks, indicating a mechanism for calcium's role in cellular contractility in EMT.