Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing.
Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing.
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DOI：
10.18632/oncotarget.4173
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发表时间：
2015-08-28
期刊：
影响因子：
--
通讯作者：
Tang MJ
中科院分区：
文献类型：
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作者：
Lin HH;Lin HK;Lin IH;Chiou YW;Chen HW;Liu CY;Harn HI;Chiu WT;Wang YK;Shen MR;Tang MJ
为了响应矩阵的刚度，要求具有刚度感知能力。在这里，我们确定了正常细胞和癌细胞是否表现出不同的机械表型。无论癌症类型是什么（乳腺癌、膀胱癌、宫颈癌、胰腺癌还是ha - rasv12转化细胞），癌细胞都比正常细胞更柔软。当在不同硬度的基质上培养时，低硬度会降低正常细胞的增殖，而癌细胞和转化细胞则失去这种反应。因此，癌细胞经历了其机械表型的变化，包括细胞软化和刚度感知的丧失。在许多肿瘤细胞和癌基因转化细胞中被抑制的Caveolin-1调节机械表型。caveolin -1上调RhoA活性和Y397FAK磷酸化指导肌动蛋白帽的形成，这与成纤维细胞的细胞弹性和刚度感知呈正相关。在正常成纤维细胞中，ha - rasv12诱导的转化和机械表型的变化可以通过重新表达caveolin-1逆转，并通过抑制caveolin-1来模拟。这是第一个描述小洞蛋白-1的新作用的研究，将机械表型与细胞转化联系起来。此外，机械特性可以作为细胞转化的生物标志物。
The stiffness sensing ability is required to respond to the stiffness of the matrix. Here we determined whether normal cells and cancer cells display distinct mechanical phenotypes. Cancer cells were softer than their normal counterparts, regardless of the type of cancer (breast, bladder, cervix, pancreas, or Ha-RasV12-transformed cells). When cultured on matrices of varying stiffness, low stiffness decreased proliferation in normal cells, while cancer cells and transformed cells lost this response. Thus, cancer cells undergo a change in their mechanical phenotype that includes cell softening and loss of stiffness sensing. Caveolin-1, which is suppressed in many tumor cells and in oncogene-transformed cells, regulates the mechanical phenotype. Caveolin-1-upregulated RhoA activity and Y397FAK phosphorylation directed actin cap formation, which was positively correlated with cell elasticity and stiffness sensing in fibroblasts. Ha-RasV12-induced transformation and changes in the mechanical phenotypes were reversed by re-expression of caveolin-1 and mimicked by the suppression of caveolin-1 in normal fibroblasts. This is the first study to describe this novel role for caveolin-1, linking mechanical phenotype to cell transformation. Furthermore, mechanical characteristics may serve as biomarkers for cell transformation.