Park Suyeon, Lee Sang Shin, Kim Shihyun, Lee Yeonjun, Park Gyeonwon, Kim Jung Oh, Choi Jongho
Department of Oral Pathology, College of Dentistry, Gangneung-Wonju National University, Korea.
Research Institute of Oral Science, College of Dentistry, Gangneung-Wonju National University, Korea.
Mol Oncol. 2025 May;19(5):1517-1531. doi: 10.1002/1878-0261.13779. Epub 2025 Jan 10.
The dynamics of focal adhesions (FAs) are essential physiological processes involved in cell spreading, metastasis, and regulation of the actin cytoskeleton. FAs are complex structures comprising proteins, such as paxillin and zyxin, which interact with extracellular membranes and influence cell motility and morphology. Although related studies have been reported in various cancers, the function and molecular mechanisms of oral squamous cell carcinoma (OSCC) remain unknown. We investigated the coordination between the actin cytoskeleton and FA proteins, specifically introducing pituitary tumor-transforming gene 1 (PTTG1; also known as PTTG1 regulator of sister chromatid separation, securin) into OSCC. Furthermore, we explored the co-localization of several FAs and PTTG1 through small interfering RNA (siRNA) control or siRNA-vasodilator-stimulated phosphoprotein (VASP) and -PTTG1, examining the mechanisms mediated by the induced changes in OSCC both in vitro and in vivo. The knockdown of VASP and PTTG1 regulates the dynamic actin cytoskeleton, restricting cell protrusion and motility from the front to the rear of OSCC cells. Our findings may provide new insights into how cells interact with each other on the surface of FAs in OSCC, influencing metastatic properties.
粘着斑（FAs）的动态变化是细胞铺展、转移及肌动蛋白细胞骨架调节过程中涉及的重要生理过程。粘着斑是由诸如桩蛋白和斑联蛋白等蛋白质组成的复杂结构，这些蛋白质与细胞外膜相互作用，影响细胞运动性和形态。尽管在各种癌症中都有相关研究报道，但口腔鳞状细胞癌（OSCC）的功能和分子机制仍不清楚。我们研究了肌动蛋白细胞骨架与粘着斑蛋白之间的协调性，具体而言是将垂体肿瘤转化基因1（PTTG1；也称为姐妹染色单体分离调节因子PTTG1，securin）导入口腔鳞状细胞癌。此外，我们通过小干扰RNA（siRNA）对照或siRNA-血管舒张刺激磷蛋白（VASP）及-PTTG1，探索了几种粘着斑与PTTG1的共定位，研究了在体外和体内由口腔鳞状细胞癌诱导变化所介导的机制。VASP和PTTG1的敲低调节了动态肌动蛋白细胞骨架，限制了口腔鳞状细胞癌细胞从前端到后端的突起和运动。我们的研究结果可能为口腔鳞状细胞癌中细胞如何在粘着斑表面相互作用并影响转移特性提供新的见解。
