Lorente Gisela, Syriani Emilio, Morales Miguel
Neurophysiology Laboratory, Deptartment of Physiological Sciences I, School of Medicine, University of Barcelona, Barcelona, Spain.
Structural Synaptic Plasticity Lab, Department of Neurodegenerative Diseases, CIBIR Piqueras 98, Logroño, La Rioja, Spain.
PLoS One. 2014 Jan 17;9(1):e85817. doi: 10.1371/journal.pone.0085817. eCollection 2014.
Cellular motility is the basis for cancer cell invasion and metastasis. In the case of breast cancer, the most common type of cancer among women, metastasis represents the most devastating stage of the disease. The central role of cellular motility in cancer development emphasizes the importance of understanding the specific mechanisms involved in this process. In this context, tumor development and metastasis would be the consequence of a loss or defect of the mechanisms that control cytoskeletal remodeling. Profilin I belongs to a family of small actin binding proteins that are thought to assist in actin filament elongation at the leading edge of migrating cells. Traditionally, Profilin I has been considered to be an essential control element for actin polymerization and cell migration. Expression of Profilin I is down-regulated in breast and various other cancer cells. In MDA-MB-231 cells, a breast cancer cell line, further inhibition of Profilin I expression promotes hypermotility and metastatic spread, a finding that contrasts with the proposed role of Profilin in enhancing polymerization. In this report, we have taken advantage of the fluorescence recovery after photobleaching (FRAP) of GFP-actin to quantify and compare actin dynamics at the leading edge level in both cancer and non-cancer cell models. Our results suggest that (i) a high level of actin dynamics (i.e., a large mobile fraction of actin filaments and a fast turnover) is a common characteristic of some cancer cells; (ii) actin polymerization shows a high degree of independence from the presence of extracellular growth factors; and (iii) our results also corroborate the role of Profilin I in regulating actin polymerization, as raising the intracellular levels of Profilin I decreased the mobile fraction ratio of actin filaments and slowed their polymerization rate; furthermore, increased Profilin levels also led to reduced individual cell velocity and directionality.
细胞运动性是癌细胞侵袭和转移的基础。在乳腺癌（女性中最常见的癌症类型）中，转移是该疾病最具毁灭性的阶段。细胞运动性在癌症发展中的核心作用凸显了理解这一过程中具体机制的重要性。在这种情况下，肿瘤发展和转移可能是控制细胞骨架重塑机制缺失或缺陷的结果。丝切蛋白I属于一类小的肌动蛋白结合蛋白家族，被认为有助于在迁移细胞的前沿延长肌动蛋白丝。传统上，丝切蛋白I被认为是肌动蛋白聚合和细胞迁移的重要控制元件。丝切蛋白I在乳腺癌细胞和其他多种癌细胞中的表达下调。在乳腺癌细胞系MDA - MB - 231细胞中，进一步抑制丝切蛋白I的表达会促进细胞的高运动性和转移扩散，这一发现与丝切蛋白在增强聚合作用方面的传统作用形成对比。在本报告中，我们利用绿色荧光蛋白标记的肌动蛋白的光漂白后荧光恢复（FRAP）技术，在癌症和非癌细胞模型中定量和比较前沿水平的肌动蛋白动力学。我们的结果表明：（i）高水平的肌动蛋白动力学（即肌动蛋白丝的大量可移动部分和快速周转）是一些癌细胞的共同特征；（ii）肌动蛋白聚合表现出高度独立于细胞外生长因子的存在；（iii）我们的结果也证实了丝切蛋白I在调节肌动蛋白聚合中的作用，因为提高细胞内丝切蛋白I的水平会降低肌动蛋白丝的可移动部分比例并减缓其聚合速率；此外，丝切蛋白水平的增加还导致单个细胞速度和方向性降低。
