Transgelin promotes lung cancer progression via activation of cancer-associated fibroblasts with enhanced IL-6 release
Chanjun Sun,
Kaishang Zhang,
Chen Ni,
Jiajia Wan,
Xixi Duan,
Xiaohan Lou,
Xiaohan Yao,
Xiangnan Li,
Ming Wang,
Zhuoyu Gu,
Pengyuan Yang,
Zhenzhen Li,
Zhihai Qin
Affiliations
Chanjun Sun
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Kaishang Zhang
Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Chen Ni
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Jiajia Wan
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Xixi Duan
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Xiaohan Lou
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Xiaohan Yao
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Xiangnan Li
Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Ming Wang
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Zhuoyu Gu
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Pengyuan Yang
Key Laboratory of Infection and Immunity of CAS, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, University of Chinese Academy of Sciences
Zhenzhen Li
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Zhihai Qin
Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University
Abstract 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.
