Davies Kerry J
Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, Castle Street, Glasgow G4 0SF, UK.
Int J Breast Cancer. 2014;2014:197480. doi: 10.1155/2014/197480. Epub 2014 Apr 7.
In the normal breast, cellular structures change cyclically in response to ovarian hormones. Cell proliferation, apoptosis, invasion, and differentiation are integral processes that are precisely regulated. Normal epithelial cells depend on the formation of intercellular adhesion contacts to form a continuous sheet of stratifying cell layers that are attached to one and other horizontally and vertically. Cells migrate by extending membrane protrusions to explore the extracellular space locating their targets in a chemotactic manner. The formation of cell protrusions is driven by the assembly of actin filaments at the leading edge. Reorganisation is regulated by a highly integrated signalling cascade that transduces extracellular stimuli to the actin filaments. This signalling cascade is governed by GTPases which act as molecular switches leading to actin polymerisation and the formation of filopodia and lamellipodia. This process is linked to downstream molecules known collectively as WASP proteins, which, in the presence of cortactin, form a complex leading to nucleation and formation of branched filaments. In breast cancer, the cortactin is over expressed leading to increased cellular motility and invasiveness. This hugely complex and integrated signalling cascade transduces extracellular stimuli. There are multiple genes related to cell motility which are dysregulated in human breast cancers.
在正常乳腺中，细胞结构会根据卵巢激素的变化而周期性改变。细胞增殖、凋亡、侵袭和分化是精确调控的重要过程。正常上皮细胞依赖细胞间黏附接触的形成，以形成连续的分层细胞层，这些细胞层在水平和垂直方向上相互连接。细胞通过延伸膜突起迁移，以趋化方式探索细胞外空间并定位其目标。细胞突起的形成是由肌动蛋白丝在前缘的组装驱动的。重组由高度整合的信号级联调节，该信号级联将细胞外刺激转导至肌动蛋白丝。该信号级联由充当分子开关的GTP酶控制，导致肌动蛋白聚合以及丝状伪足和片状伪足的形成。这个过程与统称为WASP蛋白的下游分子相关，在存在皮层肌动蛋白的情况下，它们形成一个复合物，导致分支丝的成核和形成。在乳腺癌中，皮层肌动蛋白过度表达，导致细胞运动性和侵袭性增加。这个极其复杂且整合的信号级联转导细胞外刺激。在人类乳腺癌中，有多个与细胞运动相关的基因失调。
