Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China.
Department of Biophysics, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, Sichuan, PR China; Center for Information in Biology, University of Electronic Science and Technology of China, Chengdu, 610054, Sichuan, PR China.
Biochim Biophys Acta Mol Cell Res. 2018 Jan;1865(1):172-185. doi: 10.1016/j.bbamcr.2017.10.007. Epub 2017 Oct 17.
Tumor cell can be significantly influenced by various chemical groups of the extracellular matrix proteins. However, the underlying molecular mechanisms involved in the interaction between cancer cells and functional groups in the extracellular matrix remain unknown. Using chemically modified surfaces with biological functional groups (CH, NH, OH), it was found that hydrophobic surfaces modified with CH and NH suppressed cell proliferation and induced the number of apoptotic cells. Mitochondrial dysfunction, cytochrome c release, Bax upregulation, cleaved caspase-3 and PARP, and Bcl-2 downregulation indicated that hydrophobic surfaces with CH and NH triggered the activation of intrinsic apoptotic signaling pathway. Cells on the CH- and NH-modified hydrophobic surfaces showed downregulated expression and activation of integrin β1, with a subsequent decrease of focal adhesion kinase (FAK) activity. The RhoA/ROCK/PTEN signaling was then activated to inhibit the phosphorylation of PI3K and AKT, which are essential for cell proliferation. However, pretreatment of MDA-MB-231 cells with SF1670, a PTEN inhibitor, abolished the hydrophobic surface-induced activation of the intrinsic pathway. Taken together, the present results indicate that CH- and NH-modified hydrophobic surfaces induce mitochondria-mediated apoptosis by suppressing the PTEN/PI3K/AKT pathway, but not OH surfaces. These findings are helpful to understand the interaction between extracellular matrix and cancer cells, which might provide new insights into the mechanism potential intervention strategies for tumor prognosis.
肿瘤细胞会受到细胞外基质蛋白各种化学基团的显著影响。然而，癌细胞与细胞外基质中功能基团相互作用所涉及的潜在分子机制尚不清楚。利用具有生物功能基团（CH、NH、OH）的化学改性表面，发现用 CH 和 NH 改性的疏水面会抑制细胞增殖并诱导细胞凋亡。线粒体功能障碍、细胞色素 c 释放、Bax 上调、裂解 caspase-3 和 PARP、Bcl-2 下调表明，CH 和 NH 修饰的疏水面会引发内在凋亡信号通路的激活。在 CH 和 NH 修饰的疏水面上的细胞显示出整合素 β1 的表达和激活下调，随后导致粘着斑激酶（FAK）活性降低。然后，RhoA/ROCK/PTEN 信号通路被激活，抑制了细胞增殖所必需的 PI3K 和 AKT 的磷酸化。然而，用 PTEN 抑制剂 SF1670 预处理 MDA-MB-231 细胞会消除疏水面诱导的内在途径的激活。综上所述，这些结果表明，CH 和 NH 修饰的疏水面通过抑制 PTEN/PI3K/AKT 通路诱导线粒体介导的细胞凋亡，但 OH 表面则不会。这些发现有助于理解细胞外基质与癌细胞之间的相互作用，这可能为肿瘤预后的潜在干预策略提供新的见解。
