EPLIN is a crucial regulator for extrusion of RasV12-transformed cells
EPLIN is a crucial regulator for extrusion of RasV12-transformed cells
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DOI：
10.1242/jcs.163113
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发表时间：
2015-02-15
影响因子：
4
通讯作者：
Fujita, Yasuyuki
中科院分区：
文献类型：
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作者：
Ohoka, Atsuko;Kajita, Mihoko;Fujita, Yasuyuki
在致癌的初始阶段，正常上皮层内的单个细胞发生突变。我们以前已经表明，RasV 12转化细胞被正常细胞包围时，从上皮顶端挤出。然而，这种现象背后的分子机制仍然难以捉摸。在这里，我们证明了Cav-1的微区和EPLIN（也称为LIMA 1）积累在RasV 12转化的细胞被正常细胞包围。我们还表明，敲低Cav-1或EPLIN抑制RasV 12转化细胞的顶端挤出，表明它们在消除上皮转化细胞中的积极作用。EPLIN在Cav-1的上游起作用，并影响其在被正常细胞包围的RasV 12转化细胞中的富集。此外，EPLIN调节RasV 12转化细胞中肌球蛋白II和蛋白激酶A（PKA）的非细胞自主激活。此外，EPLIN显著影响细丝蛋白A在邻近正常细胞中的积累，细丝蛋白A是上皮防御癌症（EDAC）的重要参与者，反之亦然。这些结果表明EPLIN是正常和转化上皮细胞之间相互作用的重要调节剂。
At the initial stage of carcinogenesis, a mutation occurs in a single cell within a normal epithelial layer. We have previously shown that RasV12-transformed cells are apically extruded from the epithelium when surrounded by normal cells. However, the molecular mechanisms underlying this phenomenon remain elusive. Here, we demonstrate that Cav-1-containing microdomains and EPLIN (also known as LIMA1) are accumulated in RasV12-transformed cells that are surrounded by normal cells. We also show that knockdown of Cav-1 or EPLIN suppresses apical extrusion of RasV12-transformed cells, suggesting their positive role in the elimination of transformed cells from epithelia. EPLIN functions upstream of Cav-1 and affects its enrichment in RasV12-transformed cells that are surrounded by normal cells. Furthermore, EPLIN regulates non-cell-autonomous activation of myosin-II and protein kinase A (PKA) in RasV12-transformed cells. In addition, EPLIN substantially affects the accumulation of filamin A, a vital player in epithelial defense against cancer (EDAC), in the neighboring normal cells, and vice versa. These results indicate that EPLIN is a crucial regulator of the interaction between normal and transformed epithelial cells.