Institute of Biochemistry and Biotechnology, University of the Punjab, 54590, Lahore, Pakistan.
Institute of Biochemistry and Biotechnology, University of the Punjab, 54590, Lahore, Pakistan.
Biochem Biophys Res Commun. 2019 May 21;513(1):179-185. doi: 10.1016/j.bbrc.2019.03.145. Epub 2019 Apr 2.
Extracellular signal-regulated kinase 5 (ERK5) is now considered a key regulator of breast cancer cell proliferation, migration and invasion. It is also implicated in growth factor induced anti-apoptotic signaling. But its contribution to adhesion-induced survival signaling is not clear. In the present study, using CRISPR/Cas9 editing, we knocked-out ERK5 expression in several cancer cell lines. Then MDA-MB 231 breast cancer cells lacking ERK5 were used to understand its role in adhesion-mediated cell viability. We demonstrated that ERK5 deficient cells exhibited reduced cell attachment to matrix proteins fibronectin and vitronectin. The adhesion ability of these cells was further reduced upon chemical inhibition of focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (PYK2) by PF 431396. FAK/PYK2 inhibited ERK5 knock-out cells also showed markedly reduced cell-viability and increased apoptotic signaling. This was evident from the detection of cleaved PARP and caspase 9 in these cells. Thus, our data suggests a FAK/PYK2 regulated pro-survival role of ERK5 in response to cell adhesion.
细胞外信号调节激酶 5（ERK5）现在被认为是乳腺癌细胞增殖、迁移和侵袭的关键调节因子。它还涉及生长因子诱导的抗细胞凋亡信号。但是，其在黏附诱导的存活信号中的作用尚不清楚。在本研究中，我们使用 CRISPR/Cas9 编辑敲除了几种癌细胞系中的 ERK5 表达。然后使用缺乏 ERK5 的 MDA-MB-231 乳腺癌细胞来了解其在黏附介导的细胞活力中的作用。我们证明，ERK5 缺陷细胞表现出对基质蛋白纤连蛋白和玻连蛋白的细胞附着减少。在用 PF431396 化学抑制粘着斑激酶（FAK）和富含脯氨酸的酪氨酸激酶 2（PYK2）后，这些细胞的粘附能力进一步降低。FAK/PYK2 抑制 ERK5 敲除细胞也表现出明显降低的细胞活力和增加的凋亡信号。这可以从这些细胞中 cleaved PARP 和 caspase 9 的检测中明显看出。因此，我们的数据表明，ERK5 在细胞黏附时通过 FAK/PYK2 调节了一种存活相关的作用。
Zotero 插件