Department of Biomedical Engineering, College of Medicine, Kyung Hee University, Seoul 02447, Republic of Korea.
Oncol Rep. 2023 Nov;50(5). doi: 10.3892/or.2023.8637. Epub 2023 Sep 29.
Metastasis remains a major clinical problem in cancer diagnosis and treatment. Metastasis is the leading cause of cancer‑related mortality but is still poorly understood. Cytoskeletal proteins are considered potential therapeutic targets for metastatic cancer cells because the cytoskeleton serves a key role in the migration and invasion of these cells. Vimentin and F‑actin exhibit several functional similarities and undergo quantitative and structural changes during carcinogenesis. The present study investigated the effects of vimentin and F‑actin deficiency on the survival and motility of breast cancer cells. In metastatic breast cancer cells (MDA‑MB‑231) and breast epithelial cells (MCF10A), vimentin was knocked down by small interfering RNA and F‑actin was depolymerized by latrunculin A, respectively. The effect of reduced vimentin and F‑actin content on cell viability was analyzed using the MTT assay and the proliferative capacity was compared by analyzing the recovery rate. The effect on motility was analyzed based on two processes: The distance traveled by tracking the cell nucleus and the movement of the protrusions. The effects on cell elasticity were measured using atomic force microscopy. Separately reducing vimentin or F‑actin did not effectively inhibit the growth and motility of MDA‑MB‑231 cells; however, when both vimentin and F‑actin were simultaneously deficient, MDA‑MB‑231 cells growth and migration were severely impaired. Vimentin deficiency in MDA‑MB‑231 cells was compensated by an increase in F‑actin polymerization, but no complementary action of vimentin on the decrease in F‑actin was observed. In MCF10A cells, no complementary interaction was observed for both vimentin and F‑actin.
转移仍然是癌症诊断和治疗中的一个主要临床问题。转移是癌症相关死亡的主要原因，但仍未被充分理解。细胞骨架蛋白被认为是转移性癌细胞的潜在治疗靶点，因为细胞骨架在这些细胞的迁移和侵袭中起着关键作用。波形蛋白和 F-肌动蛋白在功能上表现出许多相似之处，并在癌变过程中发生定量和结构变化。本研究探讨了波形蛋白和 F-肌动蛋白缺失对乳腺癌细胞存活和迁移的影响。在转移性乳腺癌细胞（MDA-MB-231）和乳腺上皮细胞（MCF10A）中，通过小干扰 RNA 敲低波形蛋白，用 latrunculin A 解聚 F-肌动蛋白。使用 MTT 分析检测降低的波形蛋白和 F-肌动蛋白含量对细胞活力的影响，并通过分析恢复率比较增殖能力。基于追踪细胞核和突起运动两个过程分析对运动的影响。使用原子力显微镜测量细胞弹性的影响。单独降低波形蛋白或 F-肌动蛋白并不能有效抑制 MDA-MB-231 细胞的生长和迁移；然而，当同时缺乏波形蛋白和 F-肌动蛋白时，MDA-MB-231 细胞的生长和迁移严重受损。MDA-MB-231 细胞中波形蛋白的缺失被 F-肌动蛋白聚合的增加所补偿，但没有观察到 F-肌动蛋白减少时波形蛋白的互补作用。在 MCF10A 细胞中，波形蛋白和 F-肌动蛋白均未观察到互补相互作用。
