Department of Biomedicine and Center of Cancer Biomarkers, University of Bergen, Jonas Lies vei 91, N-5009, Bergen, Norway.
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Kirkeveien 166, 0450, Oslo, Norway.
Sci Rep. 2019 Oct 25;9(1):15283. doi: 10.1038/s41598-019-51689-6.
Integrin α11β1 is a collagen-binding integrin, which is receiving increasing attention in the context of wound healing and fibrosis. Although α11β1 integrin displays similar collagen specificity to α2β1 integrin, both integrins have distinct in vivo functions. In this context, the contribution of α11 subunit cytoplasmic tail interactions to diverse molecular signals and biological functions is largely unknown. In the current study, we have deleted the α11 cytoplasmic tail and studied the effect of this deletion on α11 integrin function. Compared to wild-type cells, C2C12 cells expressing tail-less α11 attached normally to collagen I, but formed fewer focal contacts. α11-tail-less cells furthermore displayed a reduced capacity to invade and reorganize a 3D collagen matrix and to proliferate. Analysis of cell signaling showed that FAK and ERK phosphorylation was reduced in cells expressing tail-less α11. Inhibition of ERK and FAK activation decreased α11-mediated cell proliferation, whereas α11-mediated cell invasion was FAK-dependent and occurred independently of ERK signaling. In summary, our data demonstrate that the integrin α11 cytoplasmic tail plays a central role in α11 integrin-specific functions, including FAK-dependent ERK activation to promote cell proliferation.
整合素α11β1 是一种胶原结合整合素，在创伤愈合和纤维化的背景下受到越来越多的关注。尽管α11β1 整合素显示出与α2β1 整合素相似的胶原特异性，但这两种整合素在体内具有不同的功能。在这种情况下，α11 亚基胞质尾相互作用对不同分子信号和生物学功能的贡献在很大程度上是未知的。在本研究中，我们删除了α11 胞质尾，并研究了这种缺失对α11 整合素功能的影响。与野生型细胞相比，表达无尾α11 的 C2C12 细胞正常附着于 I 型胶原，但形成的焦点接触较少。α11-无尾细胞进一步显示出减少的侵袭和重组 3D 胶原基质以及增殖的能力。细胞信号分析表明，表达无尾α11 的细胞中 FAK 和 ERK 磷酸化减少。ERK 和 FAK 激活的抑制降低了α11 介导的细胞增殖，而α11 介导的细胞侵袭是 FAK 依赖性的，与 ERK 信号无关。总之，我们的数据表明，整合素α11 胞质尾在α11 整合素特异性功能中起着核心作用，包括 FAK 依赖性 ERK 激活以促进细胞增殖。
