2. Academic Validation
  3. Transgelin promotes lung cancer progression via activation of cancer-associated fibroblasts with enhanced IL-6 release

Transgelin promotes lung cancer progression via activation of cancer-associated fibroblasts with enhanced IL-6 release

  • Oncogenesis. 2023 Mar 29;12(1):18. doi: 10.1038/s41389-023-00463-5.
Chanjun Sun 1,  Kaishang Zhang 2,  Chen Ni 1,  Jiajia Wan 1,  Xixi Duan 1,  Xiaohan Lou 1,  Xiaohan Yao 1,  Xiangnan Li 2,  Ming Wang 1,  Zhuoyu Gu 1,  Pengyuan Yang 3,  Zhenzhen Li 4,  Zhihai Qin 5 6
Affiliations

Affiliations

  • 1 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 2 Thoracic Surgery Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 3 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, 100101, Beijing, China.
  • 4 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected].
  • 5 Medical Research Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450052, Henan, China. [email protected].
  • 6 Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of Biophysics, Chinese Academy of Sciences, No. 15 Datun Road, Chaoyang Area, 100101, Beijing, China. [email protected].
PMID: 36990991 DOI: 10.1038/s41389-023-00463-5
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.

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