癌关联成纤维细胞（CAFs）是异质性肿瘤微环境的主要成分，已被证实能促进肿瘤的进展；然而，其潜在机制仍然不太清楚。我们发现，与配对的正常成纤维细胞相比，从人肺癌中分离的原代CAFs中的转明蛋白（TAGLN）蛋白水平增加。肿瘤组织芯片（TMAs）显示，增加的基质TAGLN水平与肿瘤细胞的淋巴转移更相关。在一个皮下肿瘤移植模型中，在成纤维细胞中过表达Tagln也增加了小鼠体内肿瘤细胞的扩散。进一步的实验表明，Tagln过表达可促进体外成纤维细胞的激活和移动性。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。激活的成纤维细胞通过增强促炎细胞因子，特别是白细胞介素-6（IL-6）的释放促进肺癌进展。我们的研究揭示了高水平的基质TAGLN是肺癌患者的预测性风险因素。针对基质TAGLN可能提供一种抗肺癌进展的替代治疗策略。 ©2023. 作者。

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.© 2023. The Author(s).