Early stages of epithelial-to-mesenchymal transition fully enhance fibrillar migration in a Golgi-dependent manner

Worldwide, there are 7.9 million cancer-related fatalities reported every year, of which 90 percent are attributed to metastatic disease. A cell-intrinsic process, known as epithelial to mesenchymal transition (EMT), plays a significant role in metastasis. During EMT, epithelial cells acquire a high...

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Online Access:http://hdl.handle.net/2047/D20291234
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Summary:Worldwide, there are 7.9 million cancer-related fatalities reported every year, of which 90 percent are attributed to metastatic disease. A cell-intrinsic process, known as epithelial to mesenchymal transition (EMT), plays a significant role in metastasis. During EMT, epithelial cells acquire a highly motile and/or mesenchymal phenotype and invade surrounding tissue. Recent studies have also identified that cell-extrinsic fibrillar extracellular matrix cues act to guide cancer cells away from the primary tumor. While studies show that cells migrating in a fiber-like system exhibit enhanced motility in late stages of EMT, the motile properties of epithelial cells during the spectrum of EMT are unknown. Understanding the relationship between EMT and motility in a fibrillar microenvironment is critical, given that circulating tumor cells in partial states of EMT have been observed to metastasize. Furthermore, co-workers have recently shown that the Golgi may play a role in integrating different cell-intrinsic and extrinsic migration cues by stabilizing the Golgis position with respect to the nucleus (GPRN). However, it is unclear to what extent GPRN and motility are coupled throughout EMT.