低滲透壓引起的細胞脹大會造成細胞骨架的調節以及細胞膜上離子通道的活化而使得細胞體積減小。很少有文獻指出在正常細胞與癌細胞之間，體積調節是否存在著不同的細胞骨架的變化。本研究利用卵巢癌與子宮頸癌細胞為模式，想去探討受到低張溶液刺激而脹大的正常上皮細胞與癌細胞，他們之間的細胞骨架F-actin以及actin相關分子的變化是否有所不同。在低張溶液處理下，卵巢癌細胞及子宮頸癌細胞脹大並且有很明顯的細胞骨架結構改變，F-actin細胞骨架會進行重組，包括纖絲狀的F-actin減少，並在細胞周邊形成環狀的F-actin或點狀的F-actin。ezrin是一種actin結合蛋白，受到低張溶液刺激，會從細胞質跑到細胞周邊並和F-actin結合；低張溶液刺激下，也會使focal adhesion進行重組，並且增加FAK-pY397和ezrin之間的結合。我們也發現extracellular signal–regulated kinases 1 and 2 (ERK1/2)抑制劑PD98059 (50 μM)能減少F-actin、ezrin以及FAK-pY397之間的結合。相反地，正常卵巢及子宮頸上皮細胞的細胞面積調節能力較癌細胞差，他們沒有明顯的細胞骨架F-actin重組，也沒有focal adhesion的表現。綜合上述結果，本研究發現，在低張溶液刺激下而脹大的正常上皮細胞與癌細胞，他們的細胞骨架F-actin及actin相關分子有不同的變化情形。

Hypotonicity-induced cell swelling is characterized by a modulation of cytoskeletal architecture and activation of membrane ion transport, which result in regulatory volume decrease. Little is known about the possible signal differences involved in volume-regulated cytoskeletal dynamics between normal and cancer cells. By the models of ovarian and cervical cancer, my thesis aims to elucidate the dynamics of F-actin and actin-associated proteins in osmotic swelling of normal and cancer cells. In response to hypotonicity, ovarian and cervical cancer cells swelled and an obvious alteration in cellular architecture occurred. The actin cytoskeleton was remodeled to counteract cell swelling, which consisted of the reduction of the ventral stress fibers and the formation of cortical actin and F-actin patches at the cell border. In the isotonic condition, ezrin, a member of ERM family, mainly distributed in the cytosol. Hypotonicity induced the recruitment of ezrin as well as phospho-FAK Tyr397 to F-actin-enriched membrane protrusions. The converse alterations for actin network and ezrin recruitment were observed in parallel with surface area changes. Interestingly, hypotonicity-induced the interaction of F-actin, ezrin, and phospho-FAK Tyr397 was inhibited by the ERK1/ERK2 inhibitor (50 μM PD98059). These data indicate that hypotonicity-activated MAPK pathway (ERK1/ERK2) is involved the interaction between F-actin, ezrin, and phospho-FAK Tyr397. In contrast, normal epithelial cells of cervix and ovary showed poor adjustment of surface area change, no obvious F-actin remodeling, and no active focal adhesions in response to hypotonicity. Thus, this study demonstrates hypotonicity induces the different osmo-sensitive cytoskeletal remodeling between normal and cancer cells.

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