Biomedical Engineering Department, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA.
Physics Department, Worcester Polytechnic Institute, 100 Institute Road, Worcester, MA 01609, USA.
Int J Mol Sci. 2018 May 30;19(6):1613. doi: 10.3390/ijms19061613.
It has previously been shown that the simultaneous activation of PI3K (phosphatidylinositol 3-kinase) and Ras/MAPK (mitogen-activated protein kinases) pathways facilitate tumor growth despite only inducing cancer cell dormancy individually. Determining the impacts on cellular mechanics each pathway incites alone and in unison is critical to developing non-toxic cancer therapies for triple-negative breast cancers. PTEN (phosphatase and tensin homolog) knockout and activated KRAS (Kristen rat sarcoma viral oncogene homolog) overexpression in healthy MCF-10A human breast epithelial cells activated the PI3K and Ras/MAPK pathways, respectively. Cell stiffness and fluidity were simultaneously measured using atomic force microscopy. Results suggest that PTEN knockout reduced cell stiffness and increased cell fluidity independent of PI3K activation. Effects of activated KRAS overexpression on cell stiffness depends on rigidity of cell culture substrate. Activated KRAS overexpression also counteracts the effects of PTEN knockout.
先前已经表明，尽管单独诱导癌细胞休眠，但同时激活 PI3K（磷脂酰肌醇 3-激酶）和 Ras/MAPK（有丝分裂原激活的蛋白激酶）途径有助于肿瘤生长。确定每个途径单独和协同作用对细胞力学的影响对于开发用于三阴性乳腺癌的非毒性癌症疗法至关重要。PTEN（磷酸酶和张力蛋白同源物）敲除和激活的 KRAS（克莉丝汀大鼠肉瘤病毒致癌基因同源物）过表达在健康的 MCF-10A 人乳腺上皮细胞中分别激活了 PI3K 和 Ras/MAPK 途径。使用原子力显微镜同时测量了细胞硬度和流动性。结果表明，PTEN 敲除降低了细胞硬度并增加了细胞流动性，而与 PI3K 激活无关。激活的 KRAS 过表达对细胞硬度的影响取决于细胞培养底物的刚性。激活的 KRAS 过表达还抵消了 PTEN 敲除的影响。
