Cancer-associated fibroblasts (CAFs), the principal constituent of the heterogenous tumor microenvironment, have been shown to promote tumor progression; however, the underlying mechanism is still less clear. Here, we find that transgelin (TAGLN) protein levels increased in primary CAFs isolated from human lung cancer, compared with those in paired normal fibroblasts. Tumor microarrays (TMAs) revealed that increased stromal TAGLN levels correlates with more lymphatic metastasis of tumor cells. In a subcutaneous tumor transplantation model, overexpression of Tagln in fibroblasts also increased tumor cell spread in mice. Further experiments show that Tagln overexpression promoted fibroblast activation and mobility in vitro. And TAGLN facilitates p-p65 entry into the nucleus, thereby activating the NF-κB signaling pathway in fibroblasts. Activated fibroblasts promote lung cancer progression via enhancing the release of pro-inflammatory cytokines, especially interleukine-6 (IL-6). Our study revealed that the high levels of stromal TAGLN is a predictive risk factor for patients with lung cancer. Targeting stromal TAGLN may present an alternative therapeutic strategy against lung cancer progression.

癌症相关成纤维细胞 (CAF) 是异质性肿瘤微环境的主要成分，已被证明可促进肿瘤进展；然而，潜在的机制仍然不太清楚。在这里，我们发现与成对的正常成纤维细胞相比，从人类肺癌中分离出的原代 CAF 中的转运蛋白 (TAGLN) 蛋白水平增加。肿瘤微阵列 (TMAs) 显示，增加的基质 TAGLN 水平与更多的肿瘤细胞淋巴转移相关。在皮下肿瘤移植模型中，成纤维细胞中Tagln的过表达也增加了小鼠体内的肿瘤细胞扩散。进一步的实验表明，Tagln过表达促进了体外成纤维细胞的活化和移动。并且TAGLN促进p-p65进入细胞核，从而激活成纤维细胞中的NF-κB信号通路。活化的成纤维细胞通过增强促炎细胞因子，尤其是白细胞介素 6 (IL-6) 的释放来促进肺癌进展。我们的研究表明，高水平的间质 TAGLN 是肺癌患者的预测危险因素。靶向基质 TAGLN 可能是一种对抗肺癌进展的替代治疗策略。