| Summary: | 碩士 === 國立陽明大學 === 臨床醫學研究所 === 100 === Abstract
The Krüppel-like factor 4 (KLF4) is a zinc-finger transcriptional regulator that frequently deregulated in cancer. Recently, it was reported that persistent KLF4 expression in head and neck squamous cell carcinoma (HNSCC) is associated with poor prognosis, and the overexpression of KLF4 would increase HNSCC cells invasion and migration. However, an exact mechanism by which KLF4 enhances HNSCC cells movements remains unknown. Moreover, while epithelial-to-mesenchymal transition (EMT), a process to down-regulate organized epithelial cell-cell adhesion and to gain a mesenchymal phenotype to facilitate cell motility, has been well illustrated in tumor progression; our results showed that KLF4 up-regulates E-cadherin and promotes mesenchymal-to-epithelial transition (MET) in HNSCC cells instead. To study this issue, we correlated KLF4 expression with 84 motility-related gene profiles in human cancer cell lines from the National Cancer Institute drug-screening panel (NCI-60 panel), of which demonstrated possible links between KLF4 up-regulation and the formation of invadopodia, specialized membrane protrusive structures for extracellular matrix degradation. Subsequent studies validated the increase of cortactin, an important element of invadopodia, and augmented invadopodia formation with KLF4 overexpression. Furthermore, KLF4 and cortactin expressions are significantly correlated in HNSCC immunohistochemical (IHC) analysis and impact patient survival. Mechanistically, chromatin immunoprecipitation (chIP) confirmed the binding site of KLF4 on cortactin promoter region. Taken together, KLF4 up-regulates cortactin and promotes invadopodia formation, by which enhances tumor cell invasiveness in HNSCC with an EMT-independent, collective manner.
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